Effects of histamine-2 receptor blockade on lidocaine kinetics

J. Edward Jackson, John B. Bentley, Steven J. Glass, Tetsuro Fukui, A. Jay Gandolfi, John R. Plachetka

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


The hypothesis that the H2-receptor blockers cimetidine and ranitidine have different effects on the disposition of lidocaine, a microsomally metabolized drug dependent on hepatic blood flow for elimination, was tested. Six normal men received lidocaine infusions (2 mg/kg over 10 minutes) and lidocaine levels were determined by HPLC. Lidocame kinetics were studied in the untreated state (O) and in a doubleblind, double-dummy design after 2 days of placebo (P), cimetidine (C, 300 mg every 6 hours by mouth), or ranitidine (R, 160 mg every 12 hours by mouth). Model-independent kinetics were estimated by the statistical moment theory. The steady-state volume of distribution was lower after cimetidine (X ± SD: O, 156 ± 39 L; P, 156 ± 48 L; C, 123 ± 20 L; and R, 174 ± 38 L). A trend toward decreased lidocaine clearance after cimetidine was also noted (O, 1011 ± 140 ml/min; P, 1087 ± 227 ml/min; C, 886 ± 214 ml/min; and R, 1143 ± 225 ml/min). Elimination rate constants were of the same order in all four treatments. Only higher levels of α1-acid glycoprotein appeared to limit the lidocaine steady-state volume of distribution. Cimetidine and ranitidine have distinctly different effects on lidocaine kinetics in normal subjects. The absence of ranitidine effects on the disposition of lidocaine, a high-extraction, high-clearance drug, suggests that H2-receptor blockade may not decrease hepatic blood flow, and that cimetidine impairs drug elimination only by inhibition of hepatic microsomal enzymes. Such interactions are not likely to occur with ranitidine.

Original languageEnglish (US)
Pages (from-to)544-548
Number of pages5
JournalClinical Pharmacology and Therapeutics
Issue number5
StatePublished - May 1985

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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