Accession Number : ADP008816

Title :   Crossover Comparison of the Pharmacokinetics of Atropine and Pralidoxime Chloride in Sheep Using Different Autoinjector Delivery Systems.

Corporate Author : BATTELLE MEMORIAL INST COLUMBUS OH

Personal Author(s) : Olson, C. T. ; Menton, R. G. ; Kiser, R. C. ; Hobson, D. W. ; Snider, T. H.

Report Date : 13 MAY 1993

Pagination or Media Count : 10

Abstract : A study was performed at Battelle's Medical Research and Evaluation Facility to compare pharmacokinetics of atropine and pralidoxime chloride (2-PAM) in sheep following intramuscular injection with four different autoinjector systems. The experiment was a crossover study, with each of eight sheep receiving atropine and 2-PAM delivered by each of the four autoinjector systems with at least a one-week washout period between injections. The study used a Latin squares design balanced for sequence of injection, day of testing effects, and residual effects. Blood concentrations of atropine and 2-PAM were determined, and maximum concentrations (max), times to maximum concentrations (max), and areas under the blood concentration-time curves from 0 to 240 min (AUC(0-240)) were compared, and these parameters, along with absorption (ka) and elimination (kel) rate constants and apparent volumes of distribution (VdBeta), were estimated for each animal and injection system using the pharmacokinetic model which best represented the data. Animal to animal variability was significant for both atropine and 2-PAM empirically estimated and model-based C(max) and AUC (0-240).

Descriptors :   *ATROPINE, *PHARMACOKINETICS, *OXIMES, BLOOD, CHLORIDES, COMBINATORIAL ANALYSIS, CONSTANTS, DISTRIBUTION, ELIMINATION, INTRAMUSCULAR INJECTIONS, MEDICAL RESEARCH, MODELS, PARAMETERS, RATES, RESIDUALS, SEQUENCES, SHEEP, THERAPY, BIOLOGICAL ABSORPTION.

Subject Categories : Pharmacology

Distribution Statement : APPROVED FOR PUBLIC RELEASE