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Article ; Online: Dosing recommendation of nirmatrelvir/ritonavir using an integrated population pharmacokinetic analysis.

Chan, Phylinda L S / Singh, Ravi Shankar P / Cox, Donna S / Shi, Haihong / Damle, Bharat / Nicholas, Timothy

CPT: pharmacometrics & systems pharmacology

2023 Volume 12, Issue 12, Page(s) 1897–1910

Abstract: Protease inhibitor nirmatrelvir coadministered with ritonavir as a pharmacokinetic enhancer (PAXLOVID™; Pfizer Inc) became the first orally bioavailable antiviral agent granted Emergency Use Authorization in the United States in patients ≥12 years old ... ...

Abstract	Protease inhibitor nirmatrelvir coadministered with ritonavir as a pharmacokinetic enhancer (PAXLOVID™; Pfizer Inc) became the first orally bioavailable antiviral agent granted Emergency Use Authorization in the United States in patients ≥12 years old with mild to moderate coronavirus disease 2019 (COVID-19). This population pharmacokinetic analysis used pooled plasma nirmatrelvir concentrations from eight completed phase I and II/III studies to characterize nirmatrelvir pharmacokinetics when coadministered with ritonavir in adults with/without COVID-19. Influence of covariates (e.g., formulation, dose, COVID-19) was examined using a stepwise forward selection (α = 0.05) and backward elimination (α = 0.001) approach. Simulations with 5000 subjects for each age and weight group and renal function category were performed to support dosing recommendations of nirmatrelvir/ritonavir for adults with COVID-19 and guide dose adjustments for specific patient populations (e.g., renal insufficiency, pediatrics). The final model was a two-compartment model with first-order absorption, including allometric scaling of body weight and dose-dependent absorption (power function on relative bioavailability). Nirmatrelvir clearance (CL) increased proportionally to body surface area-normalized creatinine CL (nCLCR) up to 70 ml/min/1.73 m
MeSH term(s)	Adult ; Humans ; Child ; Ritonavir ; Antiviral Agents ; Benzodiazepines ; COVID-19
Chemical Substances	Ritonavir (O3J8G9O825) ; Antiviral Agents ; Benzodiazepines (12794-10-4)
Language	English
Publishing date	2023-10-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2697010-7
ISSN	2163-8306 ; 2163-8306
ISSN (online)	2163-8306
ISSN	2163-8306
DOI	10.1002/psp4.13039
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Article ; Online: A Comprehensive Review of the Clinical Pharmacokinetics, Pharmacodynamics, and Drug Interactions of Nirmatrelvir/Ritonavir.

Gerhart, Jacqueline / Cox, Donna S / Singh, Ravi Shankar P / Chan, Phylinda L S / Rao, Rohit / Allen, Richard / Shi, Haihong / Masters, Joanna C / Damle, Bharat

Clinical pharmacokinetics

2024 Volume 63, Issue 1, Page(s) 27–42

Abstract: Nirmatrelvir is a potent and selective inhibitor of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease that is used as an oral antiviral coronavirus disease 2019 (COVID-19) treatment. To sustain unbound systemic trough ... ...

Abstract	Nirmatrelvir is a potent and selective inhibitor of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease that is used as an oral antiviral coronavirus disease 2019 (COVID-19) treatment. To sustain unbound systemic trough concentrations above the antiviral in vitro 90% effective concentration value (EC
MeSH term(s)	Humans ; Ritonavir/pharmacology ; Ritonavir/therapeutic use ; Pandemics ; Drug Interactions ; COVID-19 ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Nitriles ; Drug Combinations ; Leucine ; Proline ; Lactams
Chemical Substances	nirmatrelvir and ritonavir drug combination ; Ritonavir (O3J8G9O825) ; Antiviral Agents ; Nitriles ; Drug Combinations ; Leucine (GMW67QNF9C) ; Proline (9DLQ4CIU6V) ; Lactams
Language	English
Publishing date	2024-01-04
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	197627-8
ISSN	1179-1926 ; 0312-5963
ISSN (online)	1179-1926
ISSN	0312-5963
DOI	10.1007/s40262-023-01339-y
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Article ; Online: Pregabalin Population Pharmacokinetic and Exposure-Response Analyses for Focal Onset Seizures in Children (4-16 years) and Adults, to Support Dose Recommendations in Children.

Chan, Phylinda L S / Marshall, Scott F / McFadyen, Lynn / Liu, Jing

Clinical pharmacology and therapeutics

2021 Volume 110, Issue 1, Page(s) 132–140

Abstract: Pregabalin is approved in multiple countries as adjunctive therapy for adult patients with focal onset seizures (FOS; previously termed partial onset seizures). This study used population pharmacokinetic (PK) and exposure-response (E-R) analyses from ... ...

Abstract	Pregabalin is approved in multiple countries as adjunctive therapy for adult patients with focal onset seizures (FOS; previously termed partial onset seizures). This study used population pharmacokinetic (PK) and exposure-response (E-R) analyses from pooled pregabalin concentration and efficacy data to compare pregabalin exposure and E-R relationships in pediatric and adult patients with FOS, to support pediatric dosage recommendations. A one-compartment disposition model was used, with first-order absorption and body surface area-normalized creatinine clearance on clearance. Individual pregabalin average steady-state concentrations were predicted and used in an E-R analysis of efficacy. The E-R relationship of pregabalin was similar in pediatric (4-16 years) and adult patients with FOS after accounting for differences in baseline natural log-transformed 28-day seizure rate and placebo effect. Population PK simulations showed that children aged 4-16 years and weighing ≥ 30 kg required pregabalin 2.5-10 mg/kg/day to achieve similar pregabalin exposure at steady-state to adult patients receiving the approved doses of 150-600 mg/day. For children 4-16 years weighing < 30 kg, a higher pregabalin dose of 3.5-14 mg/kg/day was required to achieve equivalent exposure at steady-state. The results support the dosage guidance provided in the pregabalin prescribing label, whereby pediatric patients (4-16 years) weighing < 30 kg should receive a 40% higher pregabalin dose (per kg of body weight) than patients weighing ≥ 30 kg to achieve similar exposure. Our combined modeling approach may provide guidance for future extrapolation assessment from adult to pediatric patients.
MeSH term(s)	Adolescent ; Adult ; Age Factors ; Aged ; Anticonvulsants/administration & dosage ; Anticonvulsants/pharmacokinetics ; Child ; Child, Preschool ; Creatinine/metabolism ; Dose-Response Relationship, Drug ; Epilepsies, Partial/drug therapy ; Female ; Humans ; Infant ; Male ; Middle Aged ; Models, Biological ; Pregabalin/administration & dosage ; Pregabalin/pharmacokinetics ; Treatment Outcome ; Young Adult
Chemical Substances	Anticonvulsants ; Pregabalin (55JG375S6M) ; Creatinine (AYI8EX34EU)
Language	English
Publishing date	2021-01-03
Publishing country	United States
Document type	Journal Article ; 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.2132
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Article ; Online: Pharmacokinetic and Pharmacodynamic Target Attainment in Adult and Pediatric Patients Following Administration of Ceftaroline Fosamil as a 5-Minute Infusion.

Riccobene, Todd A / Carrothers, Timothy J / Knebel, William / Raber, Susan / Chan, Phylinda L S

Clinical pharmacology in drug development

2021 Volume 10, Issue 4, Page(s) 420–427

Abstract: The key pharmacokinetic/pharmacodynamic (PK/PD) efficacy index for β-lactam antibiotics is the percentage of time that free drug concentrations exceed the minimum inhibitory concentration (MIC) of bacteria during each dosing interval (fT>MIC). ... ...

Abstract	The key pharmacokinetic/pharmacodynamic (PK/PD) efficacy index for β-lactam antibiotics is the percentage of time that free drug concentrations exceed the minimum inhibitory concentration (MIC) of bacteria during each dosing interval (fT>MIC). Ceftaroline fosamil, the prodrug of the β-lactam ceftaroline, was initially approved for administration as 60-minute intravenous (IV) infusions. Population PK analyses comparing exposure and PK/PD target attainment for 5-minute and 60-minute IV infusions, described here, have supported ceftaroline fosamil labeling updates to include variable infusion durations of 5 to 60 minutes in adults and children aged ≥2 months. A 2-compartment disposition PK model for ceftaroline fosamil and ceftaroline was used to predict steady-state ceftaroline exposures (maximum plasma concentrations [C
MeSH term(s)	Adolescent ; Adult ; Age Factors ; Anti-Bacterial Agents/administration & dosage ; Anti-Bacterial Agents/pharmacokinetics ; Anti-Bacterial Agents/pharmacology ; Area Under Curve ; Cephalosporins/administration & dosage ; Cephalosporins/pharmacokinetics ; Cephalosporins/pharmacology ; Child ; Child, Preschool ; Computer Simulation ; Female ; Humans ; Infant ; Infusions, Intravenous ; Male ; Microbial Sensitivity Tests ; Models, Biological ; Renal Insufficiency/physiopathology ; Ceftaroline
Chemical Substances	Anti-Bacterial Agents ; Cephalosporins
Language	English
Publishing date	2021-01-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649010-9
ISSN	2160-7648 ; 2160-763X
ISSN (online)	2160-7648
ISSN	2160-763X
DOI	10.1002/cpdd.907
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Article ; Online: Comparing Model Performance in Characterizing the PK/PD of the Anti-Myostatin Antibody Domagrozumab.

Tiwari, Abhinav / Bhattacharya, Indranil / Chan, Phylinda L S / Harnisch, Lutz

Clinical and translational science

2019 Volume 13, Issue 1, Page(s) 125–136

Abstract: Modeling and simulation provides quantitative information on target coverage for dose selection. Optimal model selection often relies on fit criteria and is not necessarily mechanistically driven. One such case is discussed where healthy volunteer data ... ...

Abstract	Modeling and simulation provides quantitative information on target coverage for dose selection. Optimal model selection often relies on fit criteria and is not necessarily mechanistically driven. One such case is discussed where healthy volunteer data of an anti-myostatin monoclonal antibody domagrozumab were used to develop different target-mediated drug disposition models; a quasi-steady state (QSS) rapid binding approximation model, a Michaelis-Menten (MM)-binding kinetics (MM-BK) model, and an MM-indirect response (MM-IDR) model. Whereas the MM-BK model was identified as optimal in fitting the data, with all parameters estimated with high precision, the QSS model also converged but was not able to capture the nonlinear decline. Although the least mechanistic model, MM-IDR, had the lowest objective function value, the MM-BK model was further developed as it provided a reasonable fit and allowed simulations regarding growth differentiation factor-8 target coverage for phase II dose selection with sufficient certainty to allow for testing of the underlying mechanistic assumptions.
MeSH term(s)	Adult ; Antibodies, Monoclonal, Humanized/administration & dosage ; Antibodies, Monoclonal, Humanized/adverse effects ; Antibodies, Monoclonal, Humanized/pharmacokinetics ; Clinical Trials, Phase II as Topic ; Computer Simulation ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Female ; Healthy Volunteers ; Humans ; Infusions, Intravenous ; Inhibitory Concentration 50 ; Male ; Models, Biological ; Myostatin/antagonists & inhibitors ; Myostatin/metabolism
Chemical Substances	Antibodies, Monoclonal, Humanized ; MSTN protein, human ; Myostatin ; domagrozumab (516MD5WQ24)
Language	English
Publishing date	2019-10-24
Publishing country	United States
Document type	Clinical Trial, Phase I ; Comparative Study ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	2433157-0
ISSN	1752-8062 ; 1752-8054
ISSN (online)	1752-8062
ISSN	1752-8054
DOI	10.1111/cts.12693
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Article ; Online: Patient Centric Microsampling to Support Paxlovid Clinical Development: Bridging and Implementation.

Wan, Katty / Kavetska, Olga / Damle, Bharat / Shi, Haihong / Cox, Donna S / Oladoyinbo, Olayide / Chan, Phylinda / Singh, Ravi Shankar P / Craft, Susan / Berthier, Erwin / Corrigan, Brian

Clinical pharmacology and therapeutics

2023 Volume 115, Issue 1, Page(s) 42–51

Abstract: Nirmatrelvir is a potent and selective severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) main protease inhibitor. Nirmatrelvir co-packaged with ritonavir (as PAXLOVID) received US Food and Drug Administration (FDA) Emergency Use Authorization ( ...

Abstract	Nirmatrelvir is a potent and selective severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) main protease inhibitor. Nirmatrelvir co-packaged with ritonavir (as PAXLOVID) received US Food and Drug Administration (FDA) Emergency Use Authorization (EUA) on December 22, 2021, as an oral treatment for coronavirus disease 2019 (COVID-19) and subsequent new drug application approval on May 25, 2023. Pharmacokinetic (PK) capillary blood sampling at-home using Tasso-M20 micro-volumetric sampling device was implemented in the program, including three phase II/III outpatient and several clinical pharmacology studies supporting the EUA. The at-home sampling complemented venous blood sampling procedures to enrich the PK dataset, to decrease the need for patients' site visit for PK sampling, and to allow different sampling approaches for flexibility and convenience. To demonstrate concordance/equivalence, bridging between venous plasma and Tasso dried blood results was conducted by comparing concentrations and derived PK parameters from both sampling approaches. In addition, a two-compartment population PK model was utilized to bridge the plasma and Tasso data by estimating the PK parameters using blood-to-plasma ratio as a slope parameter. Operational challenges were successfully managed to implement at-home PK sampling in global phase II/III trials. Sample quality was generally very good with less than 3% samples deemed as "not usable" from over 800 samples collected in all the studies. Experience gained from sites and patients will guide future broader implementations.
MeSH term(s)	United States ; Humans ; Lactams ; Leucine ; Ritonavir ; Patient-Centered Care
Chemical Substances	nirmatrelvir and ritonavir drug combination ; Lactams ; Leucine (GMW67QNF9C) ; Ritonavir (O3J8G9O825)
Language	English
Publishing date	2023-09-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	123793-7
ISSN	1532-6535 ; 0009-9236
ISSN (online)	1532-6535
ISSN	0009-9236
DOI	10.1002/cpt.3025
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Article ; Online: The use of extrapolation based on modeling and simulation to support high-dose regimens of ceftaroline fosamil in pediatric patients with complicated skin and soft-tissue infections.

Chan, Phylinda L S / McFadyen, Lynn / Quaye, Andrea / Leister-Tebbe, Heidi / Hendrick, Victoria M / Hammond, Jennifer / Raber, Susan

CPT: pharmacometrics & systems pharmacology

2021 Volume 10, Issue 6, Page(s) 551–563

Abstract: A model-informed drug development approach was used to select ceftaroline fosamil high-dose regimens for pediatric patients with complicated skin and soft-tissue infections caused by Staphylococcus aureus with a ceftaroline minimum inhibitory ... ...

Abstract	A model-informed drug development approach was used to select ceftaroline fosamil high-dose regimens for pediatric patients with complicated skin and soft-tissue infections caused by Staphylococcus aureus with a ceftaroline minimum inhibitory concentration (MIC) of 2 or 4 mg/L. Steady-state ceftaroline concentrations were simulated using a population pharmacokinetics (PK) model for ceftaroline fosamil and ceftaroline including data from 304 pediatric subjects and 944 adults. Probability of target attainment (PTA) for various simulated pediatric high-dose regimens and renal function categories were calculated based on patients achieving 35% fT>MIC (S. aureus PK/pharmacodynamic target for 2-log
MeSH term(s)	Adolescent ; Adult ; Anti-Bacterial Agents/administration & dosage ; Anti-Bacterial Agents/blood ; Anti-Bacterial Agents/pharmacokinetics ; Cephalosporins/administration & dosage ; Cephalosporins/blood ; Cephalosporins/pharmacokinetics ; Child ; Child, Preschool ; Clinical Trials as Topic ; Computer Simulation ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Microbial Sensitivity Tests ; Models, Biological ; Renal Insufficiency/blood ; Renal Insufficiency/metabolism ; Skin Diseases, Infectious/blood ; Skin Diseases, Infectious/drug therapy ; Skin Diseases, Infectious/metabolism ; Soft Tissue Infections/blood ; Soft Tissue Infections/drug therapy ; Soft Tissue Infections/metabolism ; Staphylococcal Infections/blood ; Staphylococcal Infections/drug therapy ; Staphylococcal Infections/metabolism ; Staphylococcus aureus ; Ceftaroline
Chemical Substances	Anti-Bacterial Agents ; Cephalosporins
Language	English
Publishing date	2021-05-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2697010-7
ISSN	2163-8306 ; 2163-8306
ISSN (online)	2163-8306
ISSN	2163-8306
DOI	10.1002/psp4.12608
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Article ; Online: Application of Quantitative Pharmacology Approaches in Bridging Pharmacokinetics and Pharmacodynamics of Domagrozumab From Adult Healthy Subjects to Pediatric Patients With Duchenne Muscular Disease.

Bhattacharya, Indranil / Manukyan, Zorayr / Chan, Phylinda / Heatherington, Anne / Harnisch, Lutz

Journal of clinical pharmacology

2017 Volume 58, Issue 3, Page(s) 314–326

Abstract: Domagrozumab, a monoclonal antibody that binds to myostatin, is being developed for Duchenne muscular dystrophy (DMD) boys following a first-in-human study in healthy adults. Literature reporting pharmacokinetic parameters of monoclonal antibodies ... ...

Abstract	Domagrozumab, a monoclonal antibody that binds to myostatin, is being developed for Duchenne muscular dystrophy (DMD) boys following a first-in-human study in healthy adults. Literature reporting pharmacokinetic parameters of monoclonal antibodies suggested that body-weight- and body-surface-area-adjusted clearance and volume of distribution estimates between adults and children are similar for subjects older than 6 years. Population modeling identified a Michaelis-Menten binding kinetics model to optimally characterize the target mediated drug disposition profile of domagrozumab and identified body mass index on the volume of distribution as the only significant covariate. Model parameters were predicted with high-precision pharmacokinetics (clearance 1.01 × 10
MeSH term(s)	Adolescent ; Adult ; Animals ; Antibodies, Monoclonal, Humanized/pharmacokinetics ; Antibodies, Monoclonal, Humanized/pharmacology ; Child ; Child, Preschool ; Female ; Healthy Volunteers ; Humans ; Macaca fascicularis ; Male ; Metabolic Clearance Rate ; Mice, Inbred C57BL ; Models, Biological ; Muscular Dystrophy, Duchenne/drug therapy ; Muscular Dystrophy, Duchenne/metabolism ; Myostatin/metabolism ; Rats, Wistar
Chemical Substances	Antibodies, Monoclonal, Humanized ; MSTN protein, human ; Myostatin ; domagrozumab (516MD5WQ24)
Language	English
Publishing date	2017-10-12
Publishing country	England
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	188980-1
ISSN	1552-4604 ; 0091-2700 ; 0021-9754
ISSN (online)	1552-4604
ISSN	0091-2700 ; 0021-9754
DOI	10.1002/jcph.1015
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Article ; Online: Comparative assessment of viral dynamic models for SARS-CoV-2 for pharmacodynamic assessment in early treatment trials.

Agyeman, Akosua A / You, Tao / Chan, Phylinda L S / Lonsdale, Dagan O / Hadjichrysanthou, Christoforos / Mahungu, Tabitha / Wey, Emmanuel Q / Lowe, David M / Lipman, Marc C I / Breuer, Judy / Kloprogge, Frank / Standing, Joseph F

British journal of clinical pharmacology

2022 Volume 88, Issue 12, Page(s) 5428–5433

Abstract: Pharmacometric analyses of time series viral load data may detect drug effects with greater power than approaches using single time points. Because SARS-CoV-2 viral load rapidly rises and then falls, viral dynamic models have been used. We compared ... ...

Abstract	Pharmacometric analyses of time series viral load data may detect drug effects with greater power than approaches using single time points. Because SARS-CoV-2 viral load rapidly rises and then falls, viral dynamic models have been used. We compared different modelling approaches when analysing Phase II-type viral dynamic data. Using two SARS-CoV-2 datasets of viral load starting within 7 days of symptoms, we fitted the slope-intercept exponential decay (SI), reduced target cell limited (rTCL), target cell limited (TCL) and TCL with eclipse phase (TCLE) models using nlmixr. Model performance was assessed via Bayesian information criterion (BIC), visual predictive checks (VPCs), goodness-of-fit plots, and parameter precision. The most complex (TCLE) model had the highest BIC for both datasets. The estimated viral decline rate was similar for all models except the TCL model for dataset A with a higher rate (median [range] day
MeSH term(s)	Humans ; SARS-CoV-2 ; Bayes Theorem ; Viral Load ; COVID-19 Drug Treatment
Language	English
Publishing date	2022-09-15
Publishing country	England
Document type	Journal Article
ZDB-ID	188974-6
ISSN	1365-2125 ; 0306-5251 ; 0264-3774
ISSN (online)	1365-2125
ISSN	0306-5251 ; 0264-3774
DOI	10.1111/bcp.15518
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Article ; Online: Pharmacokinetics of Oral Nirmatrelvir/Ritonavir, a Protease Inhibitor for Treatment of COVID-19, in Subjects With Renal Impairment.

Toussi, Sima S / Neutel, Joel Michael / Navarro, Jesus / Preston, Richard Alfred / Shi, Haihong / Kavetska, Olga / LaBadie, Robert R / Binks, Michael / Chan, Phylinda L S / Demers, Neil / Corrigan, Brian / Damle, Bharat

Clinical pharmacology and therapeutics

2022 Volume 112, Issue 4, Page(s) 892–900

Abstract: Nirmatrelvir coadministered with ritonavir is highly efficacious in reducing the risk of coronavirus disease 2019 (COVID-19) adverse outcomes among patients at increased risk of progression to severe disease, including patients with chronic kidney ... ...

Abstract	Nirmatrelvir coadministered with ritonavir is highly efficacious in reducing the risk of coronavirus disease 2019 (COVID-19) adverse outcomes among patients at increased risk of progression to severe disease, including patients with chronic kidney disease. Because nirmatrelvir is eliminated by the kidneys when given with ritonavir, this phase I study evaluated the effects of renal impairment on pharmacokinetics, safety, and tolerability of nirmatrelvir/ritonavir. Participants with normal renal function (n = 10) or mild, moderate, or severe renal impairment (n = 8 each) were administered a single 100-mg nirmatrelvir dose with 100 mg ritonavir given 12 hours before, together with and 12 and 24 hours after the nirmatrelvir dose. Systemic nirmatrelvir exposure increased with increasing renal impairment, with mild, moderate, and severe renal impairment groups having respective adjusted geometric mean ratio areas under the plasma concentration-time profile from time 0 extrapolated to infinite time of 124%, 187%, and 304% vs. the normal renal function group. Corresponding ratios for maximum plasma concentration were 130%, 138%, and 148%. Apparent clearance was positively correlated with estimated glomerular filtration rate, and geometric mean renal clearance values were particularly lower for the moderate (47% decrease) and severe (80% decrease) renal impairment groups vs. the normal renal function group. Nirmatrelvir/ritonavir exhibited an acceptable safety profile; treatment-related adverse events were mild in severity, and there were no significant findings regarding laboratory measurements, vital signs, or electrocardiogram assessments. These findings led to a dose reduction recommendation for nirmatrelvir/ritonavir in patients with moderate renal impairment (150/100 mg nirmatrelvir/ritonavir instead of 300/100 mg twice daily for 5 days). NCT04909853.
MeSH term(s)	Antiviral Agents/adverse effects ; COVID-19/drug therapy ; Enzyme Inhibitors ; Humans ; Protease Inhibitors ; Renal Insufficiency ; Ritonavir/adverse effects
Chemical Substances	Antiviral Agents ; Enzyme Inhibitors ; Protease Inhibitors ; Ritonavir (O3J8G9O825)
Language	English
Publishing date	2022-07-05
Publishing country	United States
Document type	Clinical Trial, Phase I ; Journal Article
ZDB-ID	123793-7
ISSN	1532-6535 ; 0009-9236
ISSN (online)	1532-6535
ISSN	0009-9236
DOI	10.1002/cpt.2688
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