Pharmacokinetics of ritodrine diastereomers in patients pregnant with singletons and twins.
OBJECTIVE
The chiral pharmacokinetics and pharmacodynamics of ritodrine in patients pregnant with singletons and twins were investigated to determine the optimal use of ritodrine.


METHODS
Eight and 20 patients with threatened preterm delivery of singletons and twins, respectively, were infused with ritodrine diastereomers. Serum concentrations of the drug were then measured using a newly developed method of chiral high-performance liquid chromatography.


RESULTS
Almost double the dosage of racemic ritodrine was required to prolong pregnancies with twins compared with those of singletons (2.20 +/- 1.06 vs. 1.24 +/- 0.36 microg/min per kilogram; p < 0.0001). The mean ratios of (-)-ritodrine to (+)-ritodrine in singleton and twin pregnancies were 1.17 +/- 0.10 and 1.16 +/- 0.10, respectively. However, the serum concentration and dosage ratio (C/D ratio) of (-)-ritodrine as significantly higher than that of (+)-ritodrine (p < 0.0001), whereas the clearance of (-)-ritodrine was significantly lower than that of (+)-ritodrine (p < 0.0001). A comparison of the gestation period (weeks) and diastereomer clearance did not reveal significant regression in the total analysis of the data obtained from singleton and twin pregnancies.


CONCLUSIONS
These results indicate that the clinical effectiveness of ritodrine diastereomers should be evaluated and that administration guidelines should be established based upon serum concentrations so that ritodrine can be more effectively administered to pregnant patients carrying either singletons or twins.
Konda
A
A
Departments of Pharmacy, Tenshi Hospital, Sapporo, Japan.
Ito
T
T
Yoshida
H
H
Toda
T
T
Hayakawa
T
T
Inotsume
N
N
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000328:Adult; D000704:Analysis of Variance; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D011247:Pregnancy; D011272:Pregnancy, Multiple; D047928:Premature Birth / Q000517:prevention & control*; D012044:Regression Analysis; D012312:Ritodrine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013237:Stereoisomerism; D015149:Tocolytic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D000318:Adrenergic beta-Agonists; D015149:Tocolytic Agents; D012312:Ritodrine