Evaluation of the pharmacodynamics and pharmacokinetics of ritodrine when administered as a loading dose. On establishing a potentially useful drug administration regimen in cases of fetal distress

Abstract

Inhibition of labor during the intrapartum period has been suggested as a method of managing acute fetal distress. In such cases, rapid tocolysis is desirable but, in high doses, beta-adrenergic-receptor agonists, such as ritodrine, may cause severe maternal hypotension that could aggravate the existing fetal distress. We undertook the present study to establish a safe infusion protocol for ritodrine that achieves high plasma concentration rapidly. Twelve nonpregnant female volunteers received, on separate days, three infusions of ritodrine, that is, 1, 2, and 3 mg, during a 2-minute period. The peak plasma concentration measured by high-performance liquid chromatography with electrochemical detection averaged 37, 74, and 100 ng/ml after the 1, 2, and 3 mg doses, respectively. Ritodrine concentrations decreased rapidly and with the 3 mg dose the ritodrine concentration was only 14 ng/ml after 15 minutes. The elimination phase half-life of ritodrine averaged 6.11 hours. None of the doses significantly affected systolic blood pressure but ritodrine increased heart rate and the plasma glucose level and decreased diastolic blood pressure and the plasma potassium concentration. Even at the highest infusion rate, the maximal changes in cardiovascular and metabolic variables were short-lived and clinically modest; heart rate increased 29 bpm, diastolic blood pressure decreased 8 mm Hg, glucose level increased 26 mg/dl, and potassium concentration decreased 0.6 mEq/L. These data indicate that high plasma concentrations of ritodrine can be achieved rapidly without serious side effects.