Currently recommended oral regimens for ritodrine tocolysis result in extremely low plasma levels

Our aim was to compare plasma drug levels in patients receiving ritodrine intravenously with those in patients receiving ritodrine orally at recommended dosages.

Plasma samples from 20 pregnant patients treated with intravenous ritodrine (50 to 300 micrograms/min), 9 patients treated with oral ritodrine only (60 to 120 mg per 24 hours), and 9 patients treated first with intravenous and subsequently with oral ritodrine were analyzed for ritodrine concentration with the use of high-performance liquid chromatography.

Average plasma ritodrine levels of patients receiving different intravenous dosages ranged from 27.8 +/- 3.5 to 113.3 +/- 38.8 ng/ml. Levels during oral therapy ranged between 9.8 +/- 3.2 and 13.8 +/- 4.4 ng/ml. In both modes of drug delivery, concentrations were significantly correlated with doses. In patients treated first with intravenous ritodrine and subsequently with the oral form, plasma concentrations during oral therapy averaged 27.7% +/- 18.8% of those obtained during intravenous infusion.

Subtherapeutic plasma concentrations might be responsible for the failure to demonstrate clinical benefits of oral ritodrine in prevention of recurrent preterm labor. A twofold to threefold increase in the maximum recommended oral dosage of ritodrine should be considered, especially for patients who had previously required relatively high intravenous infusion rates (> 100 micrograms/min).