Pharmacokinetics of nalbuphine hydrochloride extended release tablets in hemodialysis patients with exploratory effect on pruritus
| Autor: | Harry Alcorn, Carey Hines, Amale Hawi, Howard Hait, Thomas Sciascia, Jolene K. Berg |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Uremic pruritus Visual Analog Scale Visual analogue scale medicine.medical_treatment Cmax Administration Oral Nalbuphine Opioid Risk Assessment Severity of Illness Index Itch Drug Administration Schedule Pharmacokinetics Reference Values Renal Dialysis medicine Humans ESRD Dialysis Aged Analysis of Variance Dose-Response Relationship Drug business.industry Pruritus Venous blood Middle Aged medicine.disease Treatment Outcome Nephrology Anesthesia Area Under Curve Case-Control Studies Delayed-Action Preparations Hemodialysis Kidney Failure Chronic Female Patient Safety Safety business medicine.drug Research Article |
| Zdroj: | BMC Nephrology |
| ISSN: | 1471-2369 |
| Popis: | 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. Electronic supplementary material The online version of this article (doi:10.1186/s12882-015-0043-3) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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