Pharmacokinetics of promazine in patients with hepatic cirrhosis—correlation with a novel galactose single point method

Oliver Yoa‐Pu Hu, Hung‐Shang ‐S Tang, Tuzen‐Yen ‐Y Sheeng, Tung‐Chao ‐C Chen, Stephen H. Curry

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

We examined promazine pharmacokinetics in nine patients with hepatic cirrhosis and in six healthy subjects. A specific and sensitive HPLC method was used to measure promazine concentrations in plasma, plasma water (free drug), red blood cells, and urine after oral administration of promazine (2 × 50 mg tablet). There were highly significant reductions in total plasma clearance (p < 0.01), free drug total plasma clearance (p < 0.01), metabolic clearance (p < 0.01), metabolic clearance of free drug (p < 0.01), and fraction bound (p < 0.01) in the cirrhotic patients. The elimination half‐life and the area under the plasma concentration–time curve were significantly increased (p < 0.001 and p < 0.05, respectively) in the cirrhotic patients. However, the overall excreted promazine in urine, time to the promazine peak concentration, distribution half‐life, renal clearance, apparent volume of distribution, and the promazine concentration ratio between plasma and red blood cells were not different. Thus caution is needed in using promazine for patients with hepatic cirrhosis. A newly developed galactose single point (GSP) method was applied to quantitatively measure the residual liver function in cirrhosis patients and successfully correlated it with promazine elimination half‐life (r = 0.770, p < 0.01), total plasma clearance of free drug (r = 0.899, p < 0.005), metabolic clearance of free drug (r 0.902, p < 0.005), and plasma protein binding (r = 0.822, p < 0.005). GSP may be a convenient index for promazine routine dosage adjustment in patients with liver cirrhosis. Further studies are needed for developing GSP in to a routine index for drug dosage adjustment in metabolically impaired patients.

Original languageEnglish
Pages (from-to)111-114
Number of pages4
JournalJournal of Pharmaceutical Sciences
Volume84
Issue number1
DOIs
Publication statusPublished - Jan 1 1995
Externally publishedYes

ASJC Scopus subject areas

  • Pharmaceutical Science

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