Article ; Online: Pharmacokinetics of nalbuphine hydrochloride extended release tablets in hemodialysis patients with exploratory effect on pruritus.
2015 Volume 16, Page(s) 47
Abstract: ... antagonist/κ-agonist nalbuphine, administered orally as nalbuphine HCl extended release (ER) tablets in HD ... study, 15 HD patients with pruritus and 9 matched healthy subjects were enrolled. Nalbuphine HCl ER dose ... patients, and explore its effect on pruritus.: Methods: In this open-label multiple escalating dose ...
| Abstract | Background: Uremic pruritus is a common and deleterious condition among hemodialysis (HD) patients. Central gating of μ/κ opiate circuitry plays an important role in mediating and countering pruritogenic sensation. The objective of this study was to assess the safety and pharmacokinetics (PK) of the mixed μ-antagonist/κ-agonist nalbuphine, administered orally as nalbuphine HCl extended release (ER) tablets in HD patients, and explore its effect on pruritus. Methods: In this open-label multiple escalating dose study, 15 HD patients with pruritus and 9 matched healthy subjects were enrolled. Nalbuphine HCl ER dose was escalated from 30 mg QD to 240 mg BID over 15 days. A full PK profile was obtained under dialysis and non-dialysis conditions as a function of dose. Clearance during dialysis was determined by sampling dialysate and arterial/venous blood during dialysis. Pruritus severity was assessed twice daily using a Visual Analog Scale (VAS). Safety monitoring included extensive monitoring of EKG, blood pressure, and pulse oximetry. Results: In HD patients, nalbuphine concentration peaked within 4-9 hours and attained steady state within 2-3 days, with no significant accumulation. Mean half-life was 14.2 hours, mean Cmax and AUCtau ranged between 13 and 83 ng/mL and 118 and 761 ng∙h/mL, respectively, with exposure increasing in a nearly dose-proportional fashion. Exposure in HD patients was about 2-fold higher than in healthy subjects. There was no meaningful difference between exposure on dialysis and non-dialysis days with 1% or less of the dose removed by dialysis. Nalbuphine suppressed itch in a dose-dependent manner, reducing mean VAS score from 4.0 to 1.2 at 180 mg and 0.4 at 240 mg. Conclusions: Nalbuphine HCl ER tablets can be safely administered to HD patients without dose adjustment up to 240 mg BID and may hold promise in treating uremic pruritus. |
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| MeSH term(s) | Administration, Oral ; Adult ; Aged ; Analysis of Variance ; Area Under Curve ; Case-Control Studies ; Delayed-Action Preparations/administration & dosage ; Delayed-Action Preparations/pharmacokinetics ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Female ; Humans ; Kidney Failure, Chronic/diagnosis ; Kidney Failure, Chronic/therapy ; Male ; Middle Aged ; Nalbuphine/administration & dosage ; Nalbuphine/pharmacokinetics ; Patient Safety ; Pruritus/drug therapy ; Pruritus/etiology ; Reference Values ; Renal Dialysis/adverse effects ; Renal Dialysis/methods ; Risk Assessment ; Severity of Illness Index ; Treatment Outcome ; Visual Analog Scale |
| Chemical Substances | Delayed-Action Preparations ; Nalbuphine (L2T84IQI2K) |
| Language | English |
| Publishing date | 2015-04-08 |
| Publishing country | England |
| Document type | Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2041348-8 |
| ISSN | 1471-2369 ; 1471-2369 |
| ISSN (online) | 1471-2369 |
| ISSN | 1471-2369 |
| DOI | 10.1186/s12882-015-0043-3 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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