妊娠晚期接受口服阿昔洛韦抑制疗法的生殖器疱疹患者分娩时血浆阿昔洛韦水平不足。
Inadequacy of plasma acyclovir levels at delivery in patients with genital herpes receiving oral acyclovir suppressive therapy in late pregnancy.
作者信息
Leung Daniel T, Henning Paul A, Wagner Emily C, Blasig Audrey, Wald Anna, Sacks Stephen L, Corey Lawrence, Money Deborah M
机构信息
Department of Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC, Canada.
出版信息
J Obstet Gynaecol Can. 2009 Dec;31(12):1137-43. doi: 10.1016/s1701-2163(16)34374-2.
OBJECTIVE
Acyclovir therapy in late pregnancy among women with recurrent genital herpes is effective in decreasing genital lesion frequency and subclinical viral shedding rates at delivery, thereby decreasing the need for Caesarean section. Despite good adherence and increased dosing schedules, breakthrough lesions and viral shedding are still observed in some women at or near delivery. Anecdotal evidence suggests that low levels of herpes simplex virus replication at delivery may result in transmission to the neonate. Therefore, defining optimal acyclovir dosing during labour and delivery is warranted. Our objectives were to determine actual maternal and fetal acyclovir levels at delivery, and explore associations between acyclovir levels, duration of labour, and time since last acyclovir dose.
METHODS
Twenty-seven patients were prescribed oral acyclovir 400 mg three times daily from 36 weeks' gestation. Cord blood (venous and arterial) and maternal venous blood samples were collected at delivery, and acyclovir levels measured using capillary electrophoresis. Correlations between duration of labour, and time since last acyclovir dose with acyclovir blood levels were calculated.
RESULTS
Acyclovir levels were below the published mean steady-state trough value (180 ng/mL) in 52% of venous cord samples, 55% of arterial cord samples, and 36% of maternal samples. There was a significant inverse correlation between the time since last dose and venous cord levels (rs19 = -0.57, P < 0.015), arterial cord levels (rs16 = -0.63, P < 0.01), and maternal acyclovir levels (r10 = -0.69, P < 0.03).
CONCLUSION
Oral dosing of acyclovir in women in late pregnancy may result in insufficient levels at delivery to prevent viral shedding. Alternative approaches that incorporate acyclovir dosing through labour, either through oral or intravenous administration, should be evaluated to assess effects on viral shedding.
目的
对复发性生殖器疱疹女性在妊娠晚期进行阿昔洛韦治疗，可有效降低生殖器病变频率以及分娩时亚临床病毒脱落率，从而减少剖宫产的需求。尽管患者依从性良好且给药方案增加，但仍有一些女性在分娩时或临近分娩时出现突破性病变和病毒脱落。轶事证据表明，分娩时单纯疱疹病毒低水平复制可能导致新生儿感染。因此，确定分娩期间及分娩时阿昔洛韦的最佳给药剂量很有必要。我们的目标是测定分娩时母体和胎儿的阿昔洛韦实际水平，并探讨阿昔洛韦水平、产程和距上次阿昔洛韦给药时间之间的关联。
方法
27例患者自妊娠36周起每日口服阿昔洛韦400mg，分三次服用。分娩时采集脐血（静脉血和动脉血）和母体静脉血样本，采用毛细管电泳法测定阿昔洛韦水平。计算产程、距上次阿昔洛韦给药时间与阿昔洛韦血药水平之间的相关性。
结果
52%的脐静脉样本、55%的脐动脉样本和36%的母体样本中，阿昔洛韦水平低于已公布的平均稳态谷值（180ng/mL）。距上次给药时间与脐静脉水平（rs19=-0.57，P<0.015）、脐动脉水平（rs16=-0.63，P<0.01）和母体阿昔洛韦水平（r10=-0.69，P<0.03）之间存在显著负相关。
结论
妊娠晚期女性口服阿昔洛韦可能导致分娩时药物水平不足，无法预防病毒脱落。应评估通过口服或静脉给药在分娩过程中加入阿昔洛韦给药的替代方法，以评估其对病毒脱落的影响。
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