Exercise frequently is prescribed therapeutically, either on its own or combined with drugs. A drug's absorption, distribution, metabolism, and excretion can be affected by the user's anatomy and physiology, which are both changed by the myriad of complex adaptations to acute and chronic exercise. This article reviews the research that suggests exercise may influence a drug's plasma concentration, and thus its efficacy and safety.

The accumulation of lactate in muscle and blood during high-intensity exercise is negatively correlated with the duration exercise can be sustained. Removal of lactate is a key component of acute recovery between consecutive bouts of such exercise. Low-intensity exercise enhances recovery by accelerating lactate turnover in metabolically active tissues, largely mediated by blood flow to these tissues. Therefore, the purpose of this research was to clarify if L-citrulline, a nutritional supplement purported to promote vasodilation via enhanced nitric oxide availability, would augment the removal of blood lactate during active recovery (AR). L-citrulline ingestion will augment the rate of blood lactate concentration decrease during AR, reduce the oxygen-cost of submaximal exercise, and increase timeto-exhaustion and peak oxygen uptake (V_O2peak) during a test of maximal aerobic power. Healthy university students (five males & five females) participated in this double-blind, randomized, placebocontrolled study. Participants exercised on a cycle ergometer at submaximal steady-state intensities followed by progressively increasing intensity to exhaustion, 10 min of AR, and then supramaximal intensity exercise to exhaustion. Oxygen uptake was measured throughout the trial and blood lactate was sampled repeatedly during AR. The protocol elicited very high peak blood lactate concentrations after exercise (11.3 þ 1.3 mmol/L). L-citrulline supplementation did not significantly alter blood lactate kinetics during AR, the oxygen cost of exercise, V_O2peak, or time-to-exhaustion. Despite a strong theoretical basis by which L-citrulline could augment lactate removal from the blood, L-citrulline supplementation showed no effect as an exercise-recovery supplement.

A traditional focus of exercise scientists studying the interaction of drugs and exercise has been on the effects of drugs on exercise performance or functional capacity. In contrast, there is limited information available about the effects of exercise on the efficacy of drugs that have been prescribed and ingested for therapeutic reasons. Those requesting the approval for the manufacture, distribution, and sale of new drugs to the public are required to submit evidence of drug effectiveness and safety to drug regulatory bodies. But, there is no associated requirement to include among that evidence the interactions of exercise with drugs. However, the physiological adaptations to acute and chronic exercise are such that there is good reason to suspect that exercise has the potential to significantly influence drug absorption and bioavailability, drug distribution within the body, and drug elimination from the body. This paper reviews the potential for interaction between exercise and pharmacokinetics.

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