Atropine pharmacokinetics are affected by moderate hemorrhage and hypothyroidism

Atropine is used both to treat a variety of clinical disorders and as an antidote to cholinesterase poisoning. While various conditions affect the physiologic responses to atropine, little is known of the pharmacokinetics of this drug except under resting conditions. Pharmacokinetic studies were performed in mongrel dogs under two experimental conditions, moderate hemorrhage and hypothyroidism, to determine whether im absorption and elimination of atropine (0.05 mg/kg body weight) were affected by changes in hemodynamic or metabolic status. Using a randomized, crossover experimental design, it was found that during hypovolemia the mean volume of distribution was reduced by 22% (2.50 +/- 0.62 vs. 3.21 +/- 0.63 L/kg), with no changes in peak serum level, total atropine availability, elimination half-life, or whole-body clearance. Hypothyroidism was associated with a significant increase in peak serum atropine concentration (26.4 +/- 3.9 vs. 20.6 +/- 4.9 ng/ml) and drug bioavailability (48.5 +/- 8.8 vs. 30.0 +/- 10.7 ng/ml.h), while the clearance was reduced by 39% (426 +/- 34 vs. 696 +/- 187 ng/ml.min). These results suggest that atropine kinetics are not altered appreciably during moderate hemorrhage. In hypothyroidism, alterations in atropine pharmacokinetics may warrant modification of drug dose and frequency of administration.