Pharmacokinetics of orally administered ritodrine.

The oral dosing regimen for ritodrine was based in large part on kinetic data obtained in nonpregnant subjects. There are limited kinetic data after oral administration of ritodrine in pregnancy. The purpose of the present study was to compare ritodrine kinetics in pregnant and nonpregnant women, evaluate the effect of feeding on ritodrine absorption in pregnant women, and determine if the plasma concentration of ritodrine is proportional to the dose administered in nonpregnant women. Plasma concentrations after a single 20 mg dose of ritodrine were significantly greater in fasting nonpregnant women than in fasting pregnant women. The area under the concentration time curve was 1372 +/- 385 and 1001 +/- 257 ng/ml/min, respectively. In pregnant women ingesting 20 mg of ritodrine, plasma concentrations were not significantly different in the fed or fasted state; plasma concentrations peaked at 11 ng/ml and were less than 3 ng/ml within 4 hours. In nonpregnant subjects the concentration of ritodrine in plasma was proportional to the dose. After ingestion of 10, 20, or 30 mg of ritodrine, the area under the curve was 751 +/- 253, 1372 +/- 385, and 2148 +/- 571 ng/ml/min, respectively. These data indicate that ritodrine concentrations in pregnant women after a 20 mg oral dose are low. Increases in dosage will probably result in proportional increases in plasma concentration. The maximal dose of ritodrine recommended for prevention of recurrent preterm labor should be increased.

Effects of maternal ritodrine administration on neonatal renal function.

Because of its effects on the cardiovascular and renin-angiotensin systems and on fluid and electrolyte homeostasis, maternal administration of ritodrine to inhibit preterm labor may cause significant alterations in renal function in the newborn infant. We determined inulin clearance, plasma renin activity, urinary arginine vasopressin excretion, and serum and urine electrolyte concentrations and osmolalities at 12 to 36 hours of life and at 6 days of life in 15 infants whose mothers had received ritodrine and in 15 infants whose mothers did not (control infants). At the time of each study, plasma ritodrine concentrations were obtained in the infants whose mothers received ritodrine. The infants whose mothers had received ritodrine had significantly lower inulin clearances and higher plasma renin activity and urinary arginine vasopressin excretion on day 1 but not on day 6. Gestational age was inversely correlated with plasma ritodrine concentration, plasma renin activity, and urinary arginine vasopressin excretion. There were no overt clinical signs of renal failure in any of the infants, and no differences in serum and urine electrolyte values, osmolality, fractional sodium excretion, or urine flow rate were observed between the groups.