Commonly used excipients modulate UDP-glucuronosyltransferase 2B7 activity to improve nalbuphine oral bioavailability in humans

Hong Jaan Wang, Cheng Huei Hsiong, Shung Tai Ho, Min Jen Lin, Tung Yuan Shih, Pei Wei Huang, Oliver Yoa Pu Hu

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Purpose: Nalbuphine (NAL) is a potent opioid analgesic, but can only be administered by injection. The major aim of this study was to develop an oral NAL formulation employing known excipients as UDP-glucuronosyltransferase 2B7 (UGT2B7) inhibitors to improve its oral bioavailability. Methods: Twenty commonly used pharmaceutical excipients were screened in vitro by using liver microsomes to identify inhibitors of UGT2B7, the major NAL metabolic enzyme. Tween 20 and PEG 400 were potent UGT2B7 inhibitors and both were co-administered (Tween-PEG) with NAL to rats and humans for pharmacokinetic and/or pharmacodynamic analyses. Results: In animal studies, oral Tween-PEG (4 mg/kg of each) significantly increased the area under the plasma NAL concentration-time curve (AUC) and the maximal plasma concentration (Cmax) by 4- and 5-fold, respectively. The results of the pharmacodynamic analysis were in agreement with those of the pharmacokinetic analysis, and showed that Tween-PEG significantly enhanced the analgesic effects of orally administered NAL. In humans, oral Tween-PEG (240 mg of each) also increased NAL Cmax 2.5-fold, and AUC by 1.6-fold. Conclusions: Tween-PEG successfully improved oral NAL bioavailability and could formulate a useful oral dosage form for patient's convenience.

Original languageEnglish
Pages (from-to)1676-1688
Number of pages13
JournalPharmaceutical Research
Volume31
Issue number7
DOIs
Publication statusPublished - Jan 1 2014
Externally publishedYes

Fingerprint

Nalbuphine
Glucuronosyltransferase
Excipients
Biological Availability
Polysorbates
Polyethylene glycols
Pharmacodynamics
Pharmacokinetics
Area Under Curve
Plasmas
Dosage Forms
Liver Microsomes
Liver
Opioid Analgesics
Analgesics
Rats
Animals
Injections

Keywords

  • bioavailability
  • excipient
  • nalbuphine
  • pharmacodynamic
  • pharmacokinetic

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Organic Chemistry
  • Molecular Medicine
  • Pharmacology (medical)
  • Biotechnology
  • Pharmacology
  • Medicine(all)

Cite this

Commonly used excipients modulate UDP-glucuronosyltransferase 2B7 activity to improve nalbuphine oral bioavailability in humans. / Wang, Hong Jaan; Hsiong, Cheng Huei; Ho, Shung Tai; Lin, Min Jen; Shih, Tung Yuan; Huang, Pei Wei; Hu, Oliver Yoa Pu.

In: Pharmaceutical Research, Vol. 31, No. 7, 01.01.2014, p. 1676-1688.

Research output: Contribution to journalArticle

Wang, Hong Jaan ; Hsiong, Cheng Huei ; Ho, Shung Tai ; Lin, Min Jen ; Shih, Tung Yuan ; Huang, Pei Wei ; Hu, Oliver Yoa Pu. / Commonly used excipients modulate UDP-glucuronosyltransferase 2B7 activity to improve nalbuphine oral bioavailability in humans. In: Pharmaceutical Research. 2014 ; Vol. 31, No. 7. pp. 1676-1688.
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