LIVIVO - Search results -

Search results

Result 1 - 10 of total 16

Search options

Article ; Online: Integrating Forward and Reverse Translation in PBPK Modeling to Predict Food Effect on Oral Absorption of Weakly Basic Drugs.

Franco, Yesenia L / Da Silva, Lais / Charbe, Nitin / Kinvig, Hannah / Kim, Soyoung / Cristofoletti, Rodrigo

2023 Volume 40, Issue 2, Page(s) 405–418

Abstract: Introduction: Ketoconazole and posaconazole are two weakly basic broad-spectrum antifungals classified as Biopharmaceutics Classification System class II drugs, indicating that they are highly permeable, but exhibit poor solubility. As a result, oral ... ...

Abstract	Introduction: Ketoconazole and posaconazole are two weakly basic broad-spectrum antifungals classified as Biopharmaceutics Classification System class II drugs, indicating that they are highly permeable, but exhibit poor solubility. As a result, oral bioavailability and clinical efficacy can be impacted by the formulation performance in the gastrointestinal system. In this work, we have leveraged in vitro biopharmaceutics and clinical data available in the literature to build physiologically based pharmacokinetic (PBPK) models for ketoconazole and posaconazole, to determine the suitability of forward in vitro-in vivo translation for characterization of in vivo drug precipitation, and to predict food effect. Methods: A stepwise modeling approach was utilized to derive key parameters related to absorption, such as drug solubility, dissolution, and precipitation kinetics from in vitro data. These parameters were then integrated into PBPK models for the simulation of ketoconazole and posaconazole plasma concentrations in the fasted and fed states. Results: Forward in vitro-in vivo translation of intestinal precipitation kinetics for both model drugs resulted in poor predictions of PK profiles. Therefore, a reverse translation approach was applied, based on limited fitting of precipitation-related parameters to clinical data. Subsequent simulations for ketoconazole and posaconazole demonstrated that fasted and fed state PK profiles for both drugs were adequately recapitulated. Conclusion: The two examples presented in this paper show how middle-out modeling approaches can be used to predict the magnitude and direction of food effects provided the model is verified on fasted state PK data.
MeSH term(s)	Ketoconazole/pharmacokinetics ; Solubility ; Gastrointestinal Tract ; Biopharmaceutics/methods ; Antifungal Agents/pharmacology ; Administration, Oral ; Computer Simulation ; Intestinal Absorption ; Models, Biological
Chemical Substances	Ketoconazole (R9400W927I) ; Antifungal Agents
Language	English
Publishing date	2023-02-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	843063-9
ISSN	1573-904X ; 0724-8741 ; 0739-0742
ISSN (online)	1573-904X
ISSN	0724-8741 ; 0739-0742
DOI	10.1007/s11095-023-03478-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1937: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾

Article ; Online: Drug-Drug Interactions in People Living With HIV at Risk of Hepatic and Renal Impairment: Current Status and Future Perspectives.

Cottura, Nicolas / Kinvig, Hannah / Grañana-Castillo, Sandra / Wood, Adam / Siccardi, Marco

Journal of clinical pharmacology

2022 Volume 62, Issue 7, Page(s) 835–846

Abstract: Despite the advancement of antiretroviral therapy (ART) for the treatment of human immunodeficiency virus (HIV), drug-drug interactions (DDIs) remain a relevant clinical issue for people living with HIV receiving ART. Antiretroviral (ARV) drugs can be ... ...

Abstract	Despite the advancement of antiretroviral therapy (ART) for the treatment of human immunodeficiency virus (HIV), drug-drug interactions (DDIs) remain a relevant clinical issue for people living with HIV receiving ART. Antiretroviral (ARV) drugs can be victims and perpetrators of DDIs, and a detailed investigation during drug discovery and development is required to determine whether dose adjustments are necessary or coadministrations are contraindicated. Maintaining therapeutic ARV plasma concentrations is essential for successful ART, and changes resulting from potential DDIs could lead to toxicity, treatment failure, or the emergence of ARV-resistant HIV. The challenges surrounding DDI management are complex in special populations of people living with HIV, and often lack evidence-based guidance as a result of their underrepresentation in clinical investigations. Specifically, the prevalence of hepatic and renal impairment in people living with HIV are between five and 10 times greater than in people who are HIV-negative, with each condition constituting approximately 15% of non-AIDS-related mortality. Therapeutic strategies tend to revolve around the treatment of risk factors that lead to hepatic and renal impairment, such as hepatitis C, hepatitis B, hypertension, hyperlipidemia, and diabetes. These strategies result in a diverse range of potential DDIs with ART. The purpose of this review was 2-fold. First, to summarize current pharmacokinetic DDIs and their mechanisms between ARVs and co-medications used for the prevention and treatment of hepatic and renal impairment in people living with HIV. Second, to identify existing knowledge gaps surrounding DDIs related to these special populations and suggest areas and techniques to focus upon in future research efforts.
MeSH term(s)	Anti-Retroviral Agents/adverse effects ; Drug Interactions ; HIV Infections/complications ; HIV Infections/drug therapy ; Humans ; Prevalence ; Renal Insufficiency/drug therapy ; Risk Factors
Chemical Substances	Anti-Retroviral Agents
Language	English
Publishing date	2022-02-08
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	188980-1
ISSN	1552-4604 ; 0091-2700 ; 0021-9754
ISSN (online)	1552-4604
ISSN	0091-2700 ; 0021-9754
DOI	10.1002/jcph.2025
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Uf I Zs.176: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Evaluating Islatravir Administered Via Microneedle Array Patch for Long-Acting HIV Pre-exposure Prophylaxis Using Physiologically Based Pharmacokinetic Modelling.

Kinvig, Hannah / Cottura, Nicolas / Lloyd, Andrew / Frivold, Collrane / Mistilis, Jessica / Jarrahian, Courtney / Siccardi, Marco

European journal of drug metabolism and pharmacokinetics

2022 Volume 47, Issue 6, Page(s) 855–868

Abstract: Background and objectives: Technologies for long-acting administration of antiretrovirals (ARVs) for the prevention and treatment of HIV are at the forefront of research initiatives aiming to tackle issues surrounding drug adherence with the current ... ...

Abstract	Background and objectives: Technologies for long-acting administration of antiretrovirals (ARVs) for the prevention and treatment of HIV are at the forefront of research initiatives aiming to tackle issues surrounding drug adherence with the current standard of once-daily oral administration. Islatravir (ISL) is an emerging ARV that shows promising characteristics for long-acting prevention and treatment both orally as well as through alternative routes of administration. Microneedle array patches (MAPs) are a pain-free and discreet transdermal delivery technology that offer extended-release administration of nanoparticulate drugs. This study aimed to utilise physiologically based pharmacokinetic (PBPK) modelling to predict the pharmacokinetics resulting from ISL administered via MAP and to identify key MAP characteristics required to sustain effective concentrations over extended dosing intervals. Methods: A PBPK model describing the conversion of ISL to ISL-triphosphate (ISL-TP) and its whole-body disposition was developed and verified against observed clinical data for orally administered ISL in healthy adults. An intradermal PBPK model was integrated with the ISL PBPK model to predict the dose and nanoparticle release rate required for MAP administration strategies capable of achieving a minimum ISL-TP target concentration of 0.05 pmol/10 Results: The ISL PBPK model was successfully verified, with predicted vs observed ratios falling within 0.5-2-fold. ISL MAP doses ranging from 15 to 80 mg were predicted to sustain ISL-TP concentrations above the minimum target concentration at 3, 6 and 12 months after administration. Nanoparticle release rate and MAP bioavailability were found to have a major impact on whether dosing strategies achieved the criteria. Minimum doses of 15 mg and 60 mg with a nanoparticle release rate of 0.0005 h Conclusions: The ISL PBPK model successfully predicted ISL and ISL-TP pharmacokinetics across a range of orally administered regimens. The integrated intradermal PBPK model outlined optimal MAP dose and nanoparticle release rates for effective ISL-TP concentrations up to 12 months, providing justification for further investigation of ISL as a candidate for MAP administration.
MeSH term(s)	Adult ; Humans ; Pre-Exposure Prophylaxis ; Models, Biological ; Anti-Retroviral Agents/pharmacokinetics ; HIV Infections/drug therapy ; HIV Infections/prevention & control
Chemical Substances	islatravir (QPQ082R25D) ; Anti-Retroviral Agents
Language	English
Publishing date	2022-09-30
Publishing country	France
Document type	Journal Article
ZDB-ID	196729-0
ISSN	2107-0180 ; 0398-7639 ; 0378-7966
ISSN (online)	2107-0180
ISSN	0398-7639 ; 0378-7966
DOI	10.1007/s13318-022-00793-6
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1236: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: In vitro assessment of the potential for dolutegravir to affect hepatic clearance of levonorgestrel.

Roberts, Owain / Kinvig, Hannah / Owen, Andrew / Lamorde, Mohammed / Siccardi, Marco / Scarsi, Kimberly K

HIV medicine

2021 Volume 22, Issue 10, Page(s) 898–906

Abstract: Objectives: The World Health Organization recommends that all countries adopt dolutegravir-based antiretroviral therapy as the preferred regimen for all individuals living with HIV. Levonorgestrel is a commonly used hormonal contraceptive, which ... ...

Abstract	Objectives: The World Health Organization recommends that all countries adopt dolutegravir-based antiretroviral therapy as the preferred regimen for all individuals living with HIV. Levonorgestrel is a commonly used hormonal contraceptive, which undergoes drug-drug interactions with some antiretrovirals, but the potential interaction between dolutegravir and levonorgestrel has not been examined. We aimed to evaluate cytochrome P450 (CYP)-mediated levonorgestrel metabolism and quantify the effects of dolutegravir on levonorgestrel apparent intrinsic clearance (CL Methods: In vitro CYP-mediated CL Results: Levonorgestrel clearance was mediated by multiple rhCYPs, including rhCYP3A4. Under control conditions, levonorgestrel CL Conclusions: In summary, this in vitro study suggests that dolutegravir has the potential to increase hepatic clearance of levonorgestrel by inducing both CYP3A and non-CYP3A enzymes. The observed in vitro dolutegravir-levonorgestrel drug-drug interaction should be further examined in clinical studies.
MeSH term(s)	Cytochrome P-450 CYP3A ; HIV Infections/drug therapy ; Heterocyclic Compounds, 3-Ring/pharmacology ; Humans ; Levonorgestrel ; Oxazines ; Piperazines ; Pyridones
Chemical Substances	Heterocyclic Compounds, 3-Ring ; Oxazines ; Piperazines ; Pyridones ; Levonorgestrel (5W7SIA7YZW) ; dolutegravir (DKO1W9H7M1) ; Cytochrome P-450 CYP3A (EC 1.14.14.1)
Language	English
Publishing date	2021-07-30
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2001932-4
ISSN	1468-1293 ; 1464-2662
ISSN (online)	1468-1293
ISSN	1464-2662
DOI	10.1111/hiv.13136
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 5441: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article: Physiologically Based Pharmacokinetic Modelling of Cabotegravir Microarray Patches in Rats and Humans.

Kinvig, Hannah / Rajoli, Rajith K R / Pertinez, Henry / Vora, Lalitkumar K / Volpe-Zanutto, Fabiana / Donnelly, Ryan F / Rannard, Steve / Flexner, Charles / Siccardi, Marco / Owen, Andrew

Pharmaceutics

2023 Volume 15, Issue 12

Abstract: Microarray patches (MAPs) are currently under investigation as a self-administered, pain-free alternative used to achieve long-acting (LA) drug delivery. Cabotegravir is a potent antiretroviral that has demonstrated superior results over current pre- ... ...

Abstract	Microarray patches (MAPs) are currently under investigation as a self-administered, pain-free alternative used to achieve long-acting (LA) drug delivery. Cabotegravir is a potent antiretroviral that has demonstrated superior results over current pre-exposure prophylaxis (PrEP) regimens. This study aimed to apply physiologically based pharmacokinetic (PBPK) modelling to describe the pharmacokinetics of the dissolving bilayer MAP platform and predict the optimal dosing strategies for a once-weekly cabotegravir MAP. A mathematical description of a MAP was implemented into a PBPK model, and empirical models were utilised for parameter estimation. The intradermal PBPK model was verified against previously published in vivo rat data for intramuscular (IM) and MAP administration, and in vivo human data for the IM administration of LA cabotegravir. The verified model was utilised for the prediction of 300 mg, 150 mg and 75 mg once-weekly MAP administration in humans. Cabotegravir plasma concentrations >4 × protein-adjusted 90% inhibitory concentration (PA-IC
Language	English
Publishing date	2023-11-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics15122709
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Physiologically Based Pharmacokinetic Modelling to Identify Pharmacokinetic Parameters Driving Drug Exposure Changes in the Elderly.

Stader, Felix / Kinvig, Hannah / Penny, Melissa A / Battegay, Manuel / Siccardi, Marco / Marzolini, Catia

Clinical pharmacokinetics

2019 Volume 59, Issue 3, Page(s) 383–401

Abstract: Background: Medication use is highly prevalent with advanced age, but clinical studies are rarely conducted in the elderly, leading to limited knowledge regarding age-related pharmacokinetic changes.: Objective: The objective of this study was to ... ...

Abstract	Background: Medication use is highly prevalent with advanced age, but clinical studies are rarely conducted in the elderly, leading to limited knowledge regarding age-related pharmacokinetic changes. Objective: The objective of this study was to investigate which pharmacokinetic parameters determine drug exposure changes in the elderly by conducting virtual clinical trials for ten drugs (midazolam, metoprolol, lisinopril, amlodipine, rivaroxaban, repaglinide, atorvastatin, rosuvastatin, clarithromycin and rifampicin) using our physiologically based pharmacokinetic (PBPK) framework. Methods: PBPK models for all ten drugs were developed in young adults (20-50 years) following the best practice approach, before predicting pharmacokinetics in the elderly (≥ 65 years) without any modification of drug parameters. A descriptive relationship between age and each investigated pharmacokinetic parameter (peak concentration [C Results: The age-related changes in drug exposure were successfully simulated for all ten drugs. Pharmacokinetic parameters were predicted within 1.25-fold (70%), 1.5-fold (86%) and 2-fold (100%) of clinical data. AUC increased progressively by 0.9% per year throughout adulthood from the age of 20 years, which was explained by decreased clearance, while C Conclusion: The progressive decrease in hepatic and renal blood flow, as well as glomerular filtration, rate led to a reduced clearance driving exposure changes in the healthy elderly, independent of the drug.
MeSH term(s)	Aged ; Aged, 80 and over ; Aging/drug effects ; Aging/metabolism ; Anti-Bacterial Agents/pharmacokinetics ; Antibiotics, Antitubercular/pharmacokinetics ; Anticholesteremic Agents/pharmacokinetics ; Antihypertensive Agents/pharmacokinetics ; Area Under Curve ; Clinical Trials as Topic ; Factor Xa Inhibitors/pharmacokinetics ; Female ; Humans ; Hypnotics and Sedatives/pharmacokinetics ; Hypoglycemic Agents/pharmacokinetics ; Kidney/blood supply ; Kidney/drug effects ; Kidney/physiopathology ; Liver/blood supply ; Liver/drug effects ; Liver/physiopathology ; Male ; Models, Theoretical ; Regional Blood Flow/drug effects ; Regional Blood Flow/physiology ; Sensitivity and Specificity
Chemical Substances	Anti-Bacterial Agents ; Antibiotics, Antitubercular ; Anticholesteremic Agents ; Antihypertensive Agents ; Factor Xa Inhibitors ; Hypnotics and Sedatives ; Hypoglycemic Agents
Language	English
Publishing date	2019-09-30
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	197627-8
ISSN	1179-1926 ; 0312-5963
ISSN (online)	1179-1926
ISSN	0312-5963
DOI	10.1007/s40262-019-00822-9
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1246: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article: PBPK Modelling of Dexamethasone in Patients With COVID-19 and Liver Disease.

Montanha, Maiara Camotti / Cottura, Nicolas / Booth, Michael / Hodge, Daryl / Bunglawala, Fazila / Kinvig, Hannah / Grañana-Castillo, Sandra / Lloyd, Andrew / Khoo, Saye / Siccardi, Marco

Frontiers in pharmacology

2022 Volume 13, Page(s) 814134

Abstract: The aim of the study was to apply Physiologically-Based Pharmacokinetic (PBPK) modelling to predict the effect of liver disease (LD) on the pharmacokinetics (PK) of dexamethasone (DEX) in the treatment of COVID-19. A whole-body PBPK model was created to ... ...

Abstract	The aim of the study was to apply Physiologically-Based Pharmacokinetic (PBPK) modelling to predict the effect of liver disease (LD) on the pharmacokinetics (PK) of dexamethasone (DEX) in the treatment of COVID-19. A whole-body PBPK model was created to simulate 100 adult individuals aged 18-60 years. Physiological changes (e.g., plasma protein concentration, liver size, CP450 expression, hepatic blood flow) and portal vein shunt were incorporated into the LD model. The changes were implemented by using the Child-Pugh (CP) classification system. DEX was qualified using clinical data in healthy adults for both oral (PO) and intravenous (IV) administrations and similarly propranolol (PRO) and midazolam (MDZ) were qualified with PO and IV clinical data in healthy and LD adults. The qualified model was subsequently used to simulate a 6 mg PO and 20 mg IV dose of DEX in patients with varying degrees of LD, with and without shunting. The PBPK model was successfully qualified across DEX, MDZ and PRO. In contrast to healthy adults, the simulated systemic clearance of DEX decreased (35%-60%) and the plasma concentrations increased (170%-400%) in patients with LD. Moreover, at higher doses of DEX, the AUC ratio between healthy/LD individuals remained comparable to lower doses. The exposure of DEX in different stages of LD was predicted through PBPK modelling, providing a rational framework to predict PK in complex clinical scenarios related to COVID-19. Model simulations suggest dose adjustments of DEX in LD patients are not necessary considering the low dose administered in the COVID-19 protocol.
Language	English
Publishing date	2022-01-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2022.814134
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Correction to: Predicting Drug-Drug Interactions between Rifampicin and Ritonavir-Boosted Atazanavir Using PBPK Modelling.

Montanha, Maiara Camotti / Fabrega, Francesc / Howarth, Alice / Cottura, Nicolas / Kinvig, Hannah / Bunglawala, Fazila / Lloyd, Andrew / Denti, Paolo / Waitt, Catriona / Siccardi, Marco

Clinical pharmacokinetics

2022 Volume 61, Issue 11, Page(s) 1641

Language	English
Publishing date	2022-09-16
Publishing country	Switzerland
Document type	Published Erratum
ZDB-ID	197627-8
ISSN	1179-1926 ; 0312-5963
ISSN (online)	1179-1926
ISSN	0312-5963
DOI	10.1007/s40262-022-01178-3
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1246: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Effect of ageing on antiretroviral drug pharmacokinetics using clinical data combined with modelling and simulation.

Stader, Felix / Courlet, Perrine / Kinvig, Hannah / Battegay, Manuel / Decosterd, Laurent A / Penny, Melissa A / Siccardi, Marco / Marzolini, Catia

British journal of clinical pharmacology

2020 Volume 87, Issue 2, Page(s) 458–470

Abstract: Aims: The impact of ageing on antiretroviral pharmacokinetics remains uncertain, leading to missing dosing recommendations for elderly people living with human immunodeficiency virus (HIV: PLWH). The objective of this study was to investigate whether ... ...

Abstract	Aims: The impact of ageing on antiretroviral pharmacokinetics remains uncertain, leading to missing dosing recommendations for elderly people living with human immunodeficiency virus (HIV: PLWH). The objective of this study was to investigate whether ageing leads to clinically relevant pharmacokinetic changes of antiretrovirals that would support a dose adjustment based on the age of the treated PLWH. Methods: Plasma concentrations for 10 first-line antiretrovirals were obtained in PLWH ≥55 years, participating in the Swiss HIV Cohort Study, and used to proof the predictive performance of our physiologically based pharmacokinetic (PBPK) model. The verified PBPK model predicted the continuous effect of ageing on HIV drug pharmacokinetics across adulthood (20-99 years). The impact of ethnicity on age-related pharmacokinetic changes between whites and other races was statistically analysed. Results: Clinically observed concentration-time profiles of all investigated antiretrovirals were generally within the 95% confidence interval of the PBPK simulations, demonstrating the predictive power of the modelling approach used. The predicted decline in drug clearance drove age-related pharmacokinetic changes of antiretrovirals, resulting in a maximal 70% [95% confidence interval: 40%, 120%] increase in antiretrovirals exposure across adulthood. Peak concentration, time to peak concentration and apparent volume of distribution were predicted to be unaltered by ageing. There was no statistically significant difference of age-related pharmacokinetic changes between studied ethnicities. Conclusion: Dose adjustment for antiretrovirals based on the age of male and female PLWH is a priori not necessary in the absence of severe comorbidities considering the large safety margin of the current first-line HIV treatments.
MeSH term(s)	Adult ; Aged ; Aging ; Cohort Studies ; Computer Simulation ; Female ; HIV Infections/drug therapy ; Humans ; Male ; Models, Biological ; Pharmaceutical Preparations ; Pharmacokinetics
Chemical Substances	Pharmaceutical Preparations
Language	English
Publishing date	2020-06-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	188974-6
ISSN	1365-2125 ; 0306-5251 ; 0264-3774
ISSN (online)	1365-2125
ISSN	0306-5251 ; 0264-3774
DOI	10.1111/bcp.14402
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1118: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Clinical Data Combined With Modeling and Simulation Indicate Unchanged Drug-Drug Interaction Magnitudes in the Elderly.

Stader, Felix / Courlet, Perrine / Kinvig, Hannah / Penny, Melissa A / Decosterd, Laurent A / Battegay, Manuel / Siccardi, Marco / Marzolini, Catia

Clinical pharmacology and therapeutics

2020 Volume 109, Issue 2, Page(s) 471–484

Abstract: Age-related comorbidities and consequently polypharmacy are highly prevalent in the elderly, resulting in an increased risk for drug-drug interactions (DDIs). The effect of aging on DDI magnitudes is mostly uncertain, leading to missing guidance ... ...

Abstract	Age-related comorbidities and consequently polypharmacy are highly prevalent in the elderly, resulting in an increased risk for drug-drug interactions (DDIs). The effect of aging on DDI magnitudes is mostly uncertain, leading to missing guidance regarding the clinical DDI management in the elderly. Clinical data obtained in aging people living with HIV ≥ 55 years, who participated in the Swiss HIV Cohort Study, demonstrated unchanged DDI magnitudes with advanced aging for four studied DDI scenarios. These data plus published data for midazolam in the presence of clarithromycin and rifampicin in elderly individuals assessed the predictive potential of the used physiologically-based pharmacokinetic (PBPK) model to simulate DDIs in the elderly. All clinically observed data were generally predicted within the 95% confidence interval of the PBPK simulations. The verified model predicted subsequently the magnitude of 50 DDIs across adulthood (20-99 years) with 42 scenarios being only verified in adults aged 20-50 years in the absence of clinically observed data in the elderly. DDI magnitudes were not impacted by aging regardless of the involved drugs, DDI mechanism, mediators of DDIs, or the sex of the investigated individuals. The prediction of unchanged DDI magnitudes with advanced aging were proofed by 17 published, independent DDIs that were investigated in young and elderly subjects. In conclusion, this study demonstrated by combining clinically observed data with modeling and simulation that aging does not impact DDI magnitudes and thus, clinical management of DDIs can a priori be similar in aging men and women in the absence of severe comorbidities.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Aging/physiology ; Clarithromycin/adverse effects ; Clarithromycin/therapeutic use ; Cohort Studies ; Comorbidity ; Computer Simulation ; Drug Interactions/physiology ; Female ; Humans ; Male ; Midazolam/adverse effects ; Midazolam/therapeutic use ; Middle Aged ; Models, Biological ; Polypharmacy ; Prospective Studies ; Rifampin/adverse effects ; Rifampin/therapeutic use ; Young Adult
Chemical Substances	Clarithromycin (H1250JIK0A) ; Midazolam (R60L0SM5BC) ; Rifampin (VJT6J7R4TR)
Language	English
Publishing date	2020-09-18
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't
ZDB-ID	123793-7
ISSN	1532-6535 ; 0009-9236
ISSN (online)	1532-6535
ISSN	0009-9236
DOI	10.1002/cpt.2017
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 20: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

To top

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito