[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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).
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.
Journal of obstetrics and gynaecology Canada: JOGC = Journal d'obstetrique et gynecologie du Canada: JOGC 12/2009; 31(12):1137-43.
[Show abstract][Hide abstract] ABSTRACT: A sensitive plasma assay for acyclovir has been developed and validated. Acyclovir was separated from plasma components using Oasis HLB columns. Separation was obtained with no plasma interference using micellar electrokinetic chromatography (175 mM SDS) and hydroxypropyl-beta-cyclodextrin (100 mM) in 90 mM borate buffer (pH 8.8) containing 0.2% NaCl. High sensitivity was achieved by large volume sample introduction and stacking. The linear range was from 20 to 10000 ng/ml with a limit of quantitation of 20 ng/ml. This method is a viable alternative to HPLC because of its high separation and sensitivity, reproducibility, and adaptability to other nucleoside analogs.
Journal of Chromatography B 07/2002; 772(2):291-7. DOI:10.1016/S1570-0232(02)00116-2 · 2.69 Impact Factor