Ritodrine serum levels: influence of dose and route of administration

Serum levels of ritodrine were measured by radio-immunoassay both after single and during chronic administration. In 50 non-pregnant women, the maximum ritodrine levels found after a single dose of 10 mg p.o. were 7.4 +/- 4.7 (ng/ml, +/- SD, n = 10); after 20 mg p.o.: 23.8 +/- 5; after 10 mg i.m.: 30.7 +/- 8.2; after 9.3 mg i.v.: 34.7 +/- 5.5; and after 18 mg i.v.: 75.1 +/- 20.7. Ritodrine determinations during chronic intravenous infusion in 116 pregnant women, at one of the seven infusion rates, showed that the serum steady-state ritodrine levels were proportional to the infusion rates below 400 micrograms/min; above that rate the ritodrine levels flattened out. In 91 pregnant women the ritodrine serum levels were measured at one of a number of different time intervals during chronic oral administration of 5 mg (n = 52) or 10 mg (n = 39) every 4 h. During the chronic oral administration of 10 mg every 4 h, the mean ritodrine levels ranged between 14.3 ng/ml at the peak and 4.6 ng/ml just prior to the subsequent dose. For rapid and controlled tocolysis, intravenous infusion is the most appropriate method; intramuscular administration has no obvious advantage. In this respect, a daily dose of 60 mg, 6 X 10 mg, administered by oral route is probably too low; moreover, the bioavailability of the drug by this route was quite different in two volunteers. Although the absolute bioavailability of the drug was estimated in only a small group of volunteers, consistent results (around 40%) were obtained with the 20-mg oral formulation.