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- Tarning, Joel, et al.
(författare)
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Population Pharmacokinetic and Pharmacodynamic Modeling of Amodiaquine and Desethylamodiaquine in Women with Plasmodium vivax Malaria during and after Pregnancy
- 2012
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Ingår i: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 56:11, s. 5764-5773
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Tidskriftsartikel (refereegranskat)abstract
- Amodiaquine is effective for the treatment of Plasmodium vivax malaria, but there is little information on the pharmacokinetic and pharmacodynamic properties of amodiaquine in pregnant women with malaria. This study evaluated the population pharmacokinetic and pharmacodynamic properties of amodiaquine and its biologically active metabolite, desethylamodiaquine, in pregnant women with P. vivax infection and again after delivery. Twenty-seven pregnant women infected with P. vivax malaria on the Thai-Myanmar border were treated with amodiaquine monotherapy (10 mg/kg/day) once daily for 3 days. Nineteen women, with and without P. vivax infections, returned to receive the same amodiaquine dose postpartum. Nonlinear mixed-effects modeling was used to evaluate the population pharmacokinetic and pharmacodynamic properties of amodiaquine and desethylamodiaquine. Amodiaquine plasma concentrations were described accurately by lagged first-order absorption with a two-compartment disposition model followed by a three-compartment disposition of desethylamodiaquine under the assumption of complete in vivo conversion. Body weight was implemented as an allometric function on all clearance and volume parameters. Amodiaquine clearance decreased linearly with age, and absorption lag time was reduced in pregnant patients. Recurrent malaria infections in pregnant women were modeled with a time-to-event model consisting of a constant-hazard function with an inhibitory effect of desethylamodiaquine. Amodiaquine treatment reduced the risk of recurrent infections from 22.2% to 7.4% at day 35. In conclusion, pregnancy did not have a clinically relevant impact on the pharmacokinetic properties of amodiaquine or desethylamodiaquine. No dose adjustments are required in pregnancy.
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| 2. |
- van Duinen, Alex J., et al.
(författare)
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Perinatal outcomes of cesarean deliveries in Sierra Leone : A prospective multicenter observational study
- 2020
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Ingår i: International Journal of Gynecology and Obstetrics. - : Wiley. - 0020-7292 .- 1879-3479. ; 150:2, s. 213-221
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To analyze the indications for cesarean deliveries and factors associated with adverse perinatal outcomes in Sierra Leone. Methods: Between October 2016 and May 2017, patients undergoing cesarean delivery performed by medical doctors and associate clinicians in nine hospitals were included in a prospective observational study. Data were collected perioperatively, at discharge, and during home visits after 30 days. Results: In total, 1274 cesarean deliveries were included of which 1099 (86.3%) were performed as emergency surgery. Of the 1376 babies, 261 (19.0%) were perinatal deaths (53 antepartum stillbirths, 155 intrapartum stillbirths, and 53 early neonatal deaths). Indications with the highest perinatal mortality were uterine rupture (45 of 55 [81.8%]), abruptio placentae (61 of 85 [71.8%]), and antepartum hemorrhage (8 of 15 [53.3%]). In the group with cesarean deliveries performed for obstructed and prolonged labor, a partograph was filled out for 212 of 425 (49.9%). However, when completed, babies had 1.81-fold reduced odds for perinatal death (95% confidence interval 1.03–3.18, P-value 0.041). Conclusion: Cesarean deliveries in Sierra Leone are associated with an exceptionally high perinatal mortality rate of 190 per 1000 births. Late presentation in the facilities and lack of adequate fetal monitoring may be contributing factors.
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