Pharmacodynamics of transdermal granisetron in women with nausea and vomiting of pregnancy

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• 作者：Steve Caritis ; MD^a ; ^{scaritis@mail.magee.edu" class="auth_mail" title="E-mail the corresponding author} ; Yang Zhao ; PhD^c ; Hui-Jun Chen^c ; Raman Venkataramanan ; PhD^b ; ^c
• 关键词：5-hydroxytryptamine-3 receptor antagonist ; nausea and vomiting of pregnancy ; Pregnancy Unique Quantification of Emesis and Nausea scores ; transdermal
• 刊名：American Journal of Obstetrics and Gynecology
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：215
• 期：1
• 页码：93.e1-93.e4
• 全文大小：315 K

文摘

Limited options exist for women with nausea and vomiting of pregnancy (NVP) who cannot tolerate oral intake. Transdermal delivery of granisetron, a 5-hydroxytryptamine-3 receptor antagonist, provides an effective alternative for such patients.

Objective

The objective of this study was to evaluate the pharmacodynamics of granisetron administered intravenously (IV) and as a sustained release transdermal patch in women with NVP.

Study Design

We recruited 16 women with singleton gestation between 12 0/7-18 6/7 weeks who were receiving treatment for NVP and had a Pregnancy Unique Quantification of Emesis and Nausea (PUQE) score of ≥6. All consenting subjects received 1 mg of granisetron as an IV infusion over 5 minutes and blood was obtained prior to the infusion and at 10, 20, 30, and 60 minutes and at 2, 4, 6, 8, 12, and 24 hours after the start of the infusion. After a minimum washout of 48 hours after initiation of IV granisetron, a 52-cm² granisetron patch (34.3 mg) was placed on the upper arm of all subjects for 7 days. Blood was drawn prior to patch placement and daily thereafter for 9 days. The subjects were evaluated daily. The PUQE score was obtained from these subjects prior to the IV infusion and daily for 2 days after and again prior to and daily for 9 days after patch placement.

Results

Complete data were available in 15 women after IV administration and 13 women after patch placement. One woman stopped participation during the IV infusion while data were not available in 2 additional women after patch placement due to noncompliance. Peak plasma granisetron concentrations after IV and transdermal administration were similar (∼10 ng/mL). Prior to IV administration of granisetron, the PUQE score was 8.6 ± 1.8 (mean ± SD). The PUQE scores were significantly reduced for the ensuing 2 days (P < .01). The PUQE score prior to patch placement was 7.6 ± 2.4. Scores were significantly (P < .001) reduced within 1 day of patch placement and stayed significantly reduced during the ensuing 6 days of patch placement. The patch was removed on the seventh day and PUQE scores increased significantly on the third day after patch removal. No serious side effects were reported either during IV administration or patch placement.

Conclusion

Granisetron significantly improved symptoms of nausea and vomiting as gauged by the PUQE score. After IV infusion the reduction in PUQE score was observed within 1 day. When granisetron was administered as a patch, benefit likewise was seen within 1 day suggesting rapid absorption of the medication transdermally. The beneficial effect of transdermal granisetron on the PUQE score persisted for the entire 7 days during which the patch was in place. In this small cohort, the granisetron patch appeared to be efficacious in reducing the symptoms of nausea and vomiting. The patch provides another option for treating this disorder and may be particularly useful in women who cannot tolerate oral medications.