Bretylium pharmacokinetics and bioavailabilities in man with various doses and modes of administration

Edward R. Garrett*, J. Russell Green, Meir Bialer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

The pharmacokinetics and bioavailabilities of bretylium tosylate were studied in 9 male normal volunteers by 60 min constant rate intravenous infusions of 200, 300, and 400 mg, by intramuscular injection of 300 and 400 mg, by oral administration of 100, 200, and 400 mg in solution, and by oral administration of 200 mg tablets. The latter studies were repeated in the same 5 volunteers which were also studied by all modes of administration and at several doses. Intravenous studies showed a sum of 3 exponentials to characterize plasma level‐time studies with a terminal half‐life of 535±32 (S.E.M.) min (n=12). The urinary recovery of unchanged drug was 77±4(S.E.M.)(n = 14). Half‐lives within a subject were correlated and independent of dose. Intramuscular administration showed an apparent half‐life of first‐order invasion of 79±13(S.E.M.)min (n = 6) with no apparent dose dependency and a urinary recovery of unchanged drug of 95.4±3.2 (S.E.M.) per cent with a terminal half‐life similar to the intravenous studies. Oral solutions had smaller lag times of absorption [17±4(S.E.M.)min] than tablets [56±9 (S.E.M.)min] and longer apparent half‐lives of first‐order absorption [231 ± 23(S.E.M.)min] than tablets [87±15(S.E.M.)min]. The tablets had slightly greater bioavailabilities [27±2.3 (S.E.M.) per cent] than the oral solutions [22.1±2.2 (S.E.M.) per cent] but with no apparent dose dependencies. Renal clearances were the same for all modes of administration. Means±S.E.M. were 735±32, i.v., 686±38, i.m., and 623±57ml min−1, p.o. Apparent overall volumes of distribution were 589±401, i.v. and 450±671 (S.E.M.), i.m. The i.v. studies in three dogs confirmed the three‐compartment body model and the high overall volumes of distribution, had terminal half‐lives similar to humans and had renal clearances of 84, 164, and 207ml min−1 that were in excess of glomerular filtration.

Original languageEnglish
Pages (from-to)129-164
Number of pages36
JournalBiopharmaceutics and Drug Disposition
Volume3
Issue number2
DOIs
StatePublished - 1982

Keywords

  • binding
  • Bioavailabilities
  • Bretylium Tosylate Pharmacokinetics
  • Dose dependencies
  • i.m.
  • i.v.
  • Normal volunteers
  • p.o.
  • Pharmacodynamics
  • Protein

Fingerprint

Dive into the research topics of 'Bretylium pharmacokinetics and bioavailabilities in man with various doses and modes of administration'. Together they form a unique fingerprint.

Cite this