Format

Send to

Choose Destination
BMC Nephrol. 2015 Apr 8;16:47. doi: 10.1186/s12882-015-0043-3.

Pharmacokinetics of nalbuphine hydrochloride extended release tablets in hemodialysis patients with exploratory effect on pruritus.

Author information

1
A Hawi Consulting, Ridgefield, CT, USA. Ahawi@ahawi.com.
2
DaVita Clinical Research, Minneapolis, MN, USA. Harry.alcorn@davita.com.
3
DaVita Clinical Research, Minneapolis, MN, USA. Jolene.berg@davita.com.
4
PPD, Richmond, VA, USA. Carey.hines@ppdi.com.
5
Edenridge Associates LLC, Wilmington, DE, USA. howardhait@edenridgeassociates.com.
6
Trevi Therapeutics, 195 Church Street, 14th Floor, New Haven, CT, 06510, USA. Thomas.sciascia@trevitherapeutics.com.

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.

PMID:
25885112
PMCID:
PMC4392787
DOI:
10.1186/s12882-015-0043-3
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center