Aim: To determine the pharmacokinetics of ritodrine in singleton and twin pregnancies.
Methods: We treated 105 pregnant women (with singletons, n=67; with twins, n=38) with continuous infusion of ritodrine and then measured steady-state serum ritodrine concentrations using HPLC.
Results: Ritodrine clearance (mean ± SD) was significantly lower in women who delivered twins than in those who delivered singletons (1.59 ± 0.30 vs. 1.75 ± 0.43 L/h/kg; p<0.001). Serum ritodrine concentration did not differ significantly between women who delivered preterm singletons and those who delivered preterm twins (97.5 ± 61.1 vs. 89.6 ± 50.4 ng/mL; p=NS), but was significantly higher in women who delivered twins at term than in those who delivered singletons at term (85.8 ± 39.7 vs. 65.7 ± 38.7 ng/mL; p<0.001).
Conclusion: Ritodrine clearance was lower in twin pregnancies than in singleton pregnancies. The dose of ritodrine administered to maintain pregnancy should be controlled taking into account singleton or twin pregnancy.
(Jpn J Clin Pharmacol Ther 2013; 44(5): 389-394)

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Vitamin D plays an important role in bone metabolism by controlling calcium absorption in the small intestine. In Japan, active vitamin D drugs are approved for treatment of osteoporosis. Studies of teriparatide and active vitamin D coadministration are limited, and none pertain to the Japanese population. This study assessed teriparatide and active vitamin D coadministration for 28 days in a Japanese population by assessing changes in serum and urinary calcium. Subjects were to be Japanese males or postmenopausal females with osteoporosis, who were ≥55 years of age residing in Japan. Of the 30 female subjects who entered the study, 29 subjects received at least one dose of teriparatide, and 28 subjects completed the study. The study included screening, 14-day lead-in, 28-day cotreatment, and 7-day follow-up periods. Upon entering the lead-in period, subjects were administered daily, oral, active vitamin D (alfacalcidol [Alfarol^®] 1.0 μg/day) and calcium supplements; teriparatide (20 μg/day) coadministration began during the cotreatment period. There were no reports of hypercalcemia or hypercalciuria. No subjects had corrected serum calcium concentrations ≥11.0 mg/dL at 16 or 24 hours postdose during the cotreatment period or any time during the study. The highest observed serum calcium was 10.3 mg/dL at 4 hours postdose. Serum calcium concentrations (corrected and total) increased at 2, 4, and 6 hours, and returned to baseline levels at 16 and 24 hours postdose. No subject had a daily urinary calcium excretion above 0.3 g/day at any time. Findings were similar to previous studies that assessed teriparatide and native vitamin D coadministration. The risks associated with coadministration of teriparatide and active vitamin D seemed low, and there were no additional risks indicated other than those seen with native vitamin D. However, since these were findings from a clinical trial, further experience in actual clinical practice will be needed.
(Jpn J Clin Pharmacol Ther 2013; 44(5): 395-403)

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Information of adverse events associated with dietary supplements or health food, which is collected by manufacturers or healthcare facilities, is inconsistent. Therefore, a method to collect essential information from patients or consumers and evaluate the causal relationship of adverse events is necessary. We previously modified a dendritic algorithm for evaluating medication-related adverse events (Jones JK. Fam Community Health 1982; 5: 58-67) for use in dietary supplements or health food. In this study, we improved the dendritic algorithm, especially in the temporal relation between taking dietary supplements or health food and onset of adverse events, and compared to a different algorithm based on the scoring scale developed by Naranjo et al (Naranjo CA, et al. Clin Pharmacol Ther 1981; 30: 239-45). Using both algorithms, eight raters (pharmaceutical science students) assessed 200 cases of adverse events provided by the manufacturer's customer inquiry center. The κ coefficient of multi-rater reliability was 0.51 for the modified dendritic algorithm and 0.35 for the scoring scale. The time required to complete the evaluation tended to be shorter using the dendritic algorithm. In conclusion, the present results indicate that the improved dendritic algorithm may be reliable and suitable for universal usage. Pilot studies using the modified algorithm during history taking of consumers or patients to collect information on adverse events are needed to assess the utility of the algorithm in clinical practice.
(Jpn J Clin Pharmacol Ther 2013; 44(5): 405-410)

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[in Japanese]

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