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Pharmacokinetics of ritodrine diastereomers in patients pregnant with singletons and twins

  • Pharmacokinetics and Disposition
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Abstract

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 μg/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.

Conclusion

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.

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Acknowledgments

This study was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Authors and Affiliations

  1. Departments of Pharmacy, Tenshi Hospital, Sapporo, Japan

    A. Konda & T. Ito

  2. Obstetrics and Gynecology, Tenshi Hospital, Sapporo, Japan

    H. Yoshida

  3. Division of Clinical Pharmacokinetics, Hokkaido Pharmaceutical University School of Pharmacy, 7-1 Katsuraoka, Otaru, 047-0264, Japan

    A. Konda, T. Toda, T. Hayakawa & N. Inotsume

Authors
  1. A. Konda
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  2. T. Ito
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  3. H. Yoshida
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  4. T. Toda
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  5. T. Hayakawa
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  6. N. Inotsume
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Corresponding author

Correspondence to N. Inotsume.

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Konda, A., Ito, T., Yoshida, H. et al. Pharmacokinetics of ritodrine diastereomers in patients pregnant with singletons and twins. Eur J Clin Pharmacol 65, 913–917 (2009). https://doi.org/10.1007/s00228-009-0665-0

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  • DOI: https://doi.org/10.1007/s00228-009-0665-0

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