The effect of exercise on atropine pharmacokinetics

Summary

Seven healthy males (19–32 y) underwent each of four separate conditions in a repeated measures design. Five of these subjects underwent an additional trial. In four of five trials subjects received 2.0 mg atropine sulfate intramuscularly in the anterolateral portion of the left thigh: at rest (T1); following completion of a single exercise (Ex) bout (T2), (Each bout consisted of 25 min of stationary cycling at 40% VO₂ max with 5 min of seated rest), prior to three Ex bouts (T3) and following one and prior to three Ex bouts (T5). Trial 4 (T4) was the same as T3 with the substitution of a saline placebo. Serum samples were collected over a 12 h period and atropine concentration was determined by RIA. Ex trials were compared to T1.

Ex prior to atropine (T2) significantly decreased the mean volume of distribution (V_z, 278 vs 2321). Ex in T3 significantly decreased the serum half life (t_1/2, 4.2 vs 3.5 h), V_z (278 vs 1981), and clearance (CL, 763 vs 638 ml·min⁻¹) and significantly increased the peak concentration (Cp, 6.7 vs 12.3 ng·ml⁻¹) and area under the curve (AUC, 44.1 vs 53.1 ng·ml⁻¹). In T5, Ex significantly decreased the t_1/2 (3.4 h), V_z (182 l) and CL (575 ml·min⁻¹) and significantly increased the absorption rate constant (ka, 0.482 vs 1.1 min⁻¹), elimination rate constant (ke, 0.0012 vs 0.0015 min⁻¹), C_p (14 ng·ml⁻¹) and AUC (53.3 ng·h·ml⁻¹).

These results demonstrate that moderate Ex either prior to and/or immediately following drug administration has the capacity to significantly modify atropine pharmacokinetics.