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The pharmacokinetics of atropine and diazepam in sheep: Intramuscular co‐administration
Author(s) -
Moore David H.,
Smallridge Robert C.,
Von Bredow Jurgen D.,
Lukey Brian J.
Publication year - 1991
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510120706
Subject(s) - atropine , diazepam , pharmacokinetics , crossover study , absorption (acoustics) , chemistry , radioimmunoassay , pharmacology , anesthesia , parasympatholytic , medicine , endocrinology , physics , alternative medicine , pathology , acoustics , placebo , muscarinic acetylcholine receptor , receptor
The purpose of this study was to determine whether the co‐administration of atropine and diazepam affect the rate and extent of absorption of either drug. A triple crossover pharmacokinetic study using adult sheep was conducted. Each of nine animals received single injections of atropine (2mg), diazepam (10mg), and a combination of the two compounds weekly over a 3‐week period. The combination of the drugs was injected into a single intramuscular site through a specially designed tandem syringe. Blood samples were obtained from time 0 to 300 min post‐injection. Serum samples were analyzed for atropine by radioimmunoassay and for diazepam by gas chromatography/mass spectrometry. Pharmacokinetic parameters were evaluated by non‐compartmental analysis. The co‐administration of atropine and diazepam intramuscularly in sheep caused a delay in the time to reach maximal concentration of atropine. However, at the time when a single injection of atropine reached its maximum serum concentration, 92 per cent of that concentration was reached by atropine in the presence of diazepam. Additionally, no difference was detected in the rate or extent of diazepam absorption when administered intramuscularly in combination with atropine at the same site.