Pharmacokinetics of quinine and its metabolites in pregnant Sudanese women with uncomplicated Plasmodium falciparum malaria

Abdelrahim, Ishraga I.; Adam, Ishag; ElGhazali, Gehad; Gustafsson, Lars L.; Elbashir, Mustafa I.; Mirghani, Rajaa A.

doi:10.1111/j.1365-2710.2007.00788.x

Cited by 32 publications

(31 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the case of propranolol, mean elimination half-life in pregnancy was shorter in both studies, but the exposure parameter (AUC) changes were not consistent; non-significant increase in the AUC [218] versus non-significant decrease in AUC [219]. Consistent but non-significant increase in Cl was reported for quinine [189,220–222]. Plasma folate concentrations showed no statistically significant changes [221,222], but conflicting change directions were seen in the mean values, depending on the dose [222].…”

Section: Resultsmentioning

confidence: 86%

Pregnancy-Associated Changes in Pharmacokinetics: A Systematic Review

et al. 2016

View full text Add to dashboard Cite

BackgroundWomen are commonly prescribed a variety of medications during pregnancy. As most organ systems are affected by the substantial anatomical and physiological changes that occur during pregnancy, it is expected that pharmacokinetics (PK) (absorption, distribution, metabolism, and excretion of drugs) would also be affected in ways that may necessitate changes in dosing schedules. The objective of this study was to systematically identify existing clinically relevant evidence on PK changes during pregnancy.Methods and FindingsSystematic searches were conducted in MEDLINE (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (Ovid), and Web of Science (Thomson Reuters), from database inception to August 31, 2015. An update of the search from September 1, 2015, to May 20, 2016, was performed, and relevant data were added to the present review. No language or date restrictions were applied. All publications of clinical PK studies involving a group of pregnant women with a comparison to nonpregnant participants or nonpregnant population data were eligible to be included in this review. A total of 198 studies involving 121 different medications fulfilled the inclusion criteria. In these studies, commonly investigated drug classes included antiretrovirals (54 studies), antiepileptic drugs (27 studies), antibiotics (23 studies), antimalarial drugs (22 studies), and cardiovascular drugs (17 studies). Overall, pregnancy-associated changes in PK parameters were often observed as consistent findings among many studies, particularly enhanced drug elimination and decreased exposure to total drugs (bound and unbound to plasma proteins) at a given dose. However, associated alterations in clinical responses and outcomes, or lack thereof, remain largely unknown.ConclusionThis systematic review of pregnancy-associated PK changes identifies a significant gap between the accumulating knowledge of PK changes in pregnant women and our understanding of their clinical impact for both mother and fetus. It is essential for clinicians to be aware of these unique pregnancy-related changes in PK, and to critically examine their clinical implications.

show abstract

Section: Resultsmentioning

confidence: 86%

Pregnancy-Associated Changes in Pharmacokinetics: A Systematic Review

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Quantification was performed using selected reaction monitoring (SRM) for the transitions m/z 356 -283 and 328 -283 for amodiaquine and desethylamodiaquine, respectively, and 336 -247 for the internal standard hydroxychloroquine. Total assay coefficients of variation (CV) for amodiaquine and desethylamodiaquine during analysis were less than 15% at all quality control levels (1,5,8,25, and 80 ng/ml for amodiaquine and 2, 10, 16, 50, and 400 ng/ml for desethylamodiaquine). The lower limit of quantification (LLOQ) was set to 1 ng/ml and 2 ng/ml for amodiaquine and desethylamodiaquine, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…A noncompartmental analysis of amodiaquine and desethylamodiaquine reported no significant pharmacokinetic difference in pregnant women and postpartum women (48). Studies in pregnant women with malaria reported relatively unchanged pharmacokinetic properties of chloroquine and quinine (1,27). However, a recent publication reported significantly lower exposure of both chloroquine and its active metabolite, desethylchloroquine, when administered as intermittent presumptive treatment in pregnancy for malaria (24).…”

mentioning

confidence: 97%

Population Pharmacokinetic and Pharmacodynamic Modeling of Amodiaquine and Desethylamodiaquine in Women with Plasmodium vivax Malaria during and after Pregnancy

Tärning

Chotsiri

Jullien

et al. 2012

Antimicrob Agents Chemother

View full text Add to dashboard Cite

f 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 mixedeffects 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. The total global annual burden of P. vivax infections has been estimated at between 80 and 400 million cases, and about 3 billion people are at risk, mainly in Central and Southeast Asia (91%) (7,16). Approximately 93 million pregnancies occur in areas where P. vivax is endemic, of which 40 million are in temperate regions with P. vivax transmission only (i.e., no P. falciparum transmission) (12). Vivax malaria rarely causes mortality but is associated with multiple relapses, anemia, abortion, and a reduction in birth weight in pregnant women with malaria (5, 32, 39, 47). Pregnant women with P. vivax infections are also more likely to experience relapses than nonpregnant women (39). Low birth weight increases the risk of infant mortality and may also have adverse consequences in the longer term (13).Relapses of P. vivax arise from dormant liver stages (i.e., hypnozoites). Primaquine is the only generally available antimalarial drug with a parasiticidal effect on this dormant liver stage of the pathogen (61). However, primaquine may cause hemolysis and is not considered safe in the treatment of P. vivax malaria during pregnancy (42). Chloroquine has traditionally been used as prophylaxis and treatment of P. vivax malaria during pregnancy, but the increasing prevalen...

show abstract

“…Whereas blood chloroquine and quinine concentrations are relatively unaffected (1,25), artesunate, artemether, dihydroartemisinin, sulfadoxine, atovaquone, proguanil, and cycloguanil concentrations are all reduced in later pregnancy (14,(30)(31)(32)(33). The reductions are often substantial, and as a result, antimalarial cure rates in pregnancy for any given antimalarial drug tend to be lower (24,34).…”

mentioning

confidence: 99%

Population Pharmacokinetics of Lumefantrine in Pregnant Women Treated with Artemether-Lumefantrine for Uncomplicated Plasmodium falciparum Malaria

Tärning

McGready

Lindegårdh

et al. 2009

Antimicrob Agents Chemother

114

View full text Add to dashboard Cite

Artemether-lumefantrine has become one of the most widely used antimalarial drugs in the world. The objective of this study was to determine the population pharmacokinetic properties of lumefantrine in pregnant women with uncomplicated multidrug-resistant Plasmodium falciparum malaria on the northwestern border of Thailand. Burmese and Karen women (n ‫؍‬ 103) with P. falciparum malaria and in the second and third trimesters of pregnancy were treated with artemether-lumefantrine (80/480 mg) twice daily for 3 days. All patients provided five capillary plasma samples for drug quantification, and the collection times were randomly distributed over 14 days. The concentration-time profiles of lumefantrine were assessed by nonlinear mixed-effects modeling. The treatment failure rate (PCR-confirmed recrudescent infections at delivery) was high; 16.5% (95% confidence interval, 9.9 to 25.1). The population pharmacokinetics of lumefantrine were described well by a two-compartment open model with first-order absorption and elimination. The final model included interindividual variability in all pharmacokinetic parameters and a linear covariate relationship between the estimated gestational age and the central volume of distribution. A high proportion of all women (40%, 41/103) had day 7 capillary plasma concentrations of <355 ng/ml (which corresponds to approximately <280 ng/ml in venous plasma), a threshold previously associated with an increased risk of therapeutic failure in nonpregnant patients in this area. Predictive modeling suggests that a twice-daily regimen given for 5 days would be preferable in later pregnancy. In conclusion, altered pharmacokinetic properties of lumefantrine contribute to the high rates of failure of artemether-lumefantrine treatment in later pregnancy. Dose optimization is urgently needed.Pregnancy has considerable effects on the pharmacokinetic properties of many of the drugs used to treat uncomplicated Plasmodium falciparum malaria. Whereas blood chloroquine and quinine concentrations are relatively unaffected (1, 25), artesunate, artemether, dihydroartemisinin, sulfadoxine, atovaquone, proguanil, and cycloguanil concentrations are all reduced in later pregnancy (14,(30)(31)(32)(33). The reductions are often substantial, and as a result, antimalarial cure rates in pregnancy for any given antimalarial drug tend to be lower (24, 34). Unfortunately, pregnant women are especially vulnerable to malaria and the fetus is adversely affected.The fixed combination of artemether and lumefantrine is the result of research undertaken by Chinese scientists and has become the most widely used coformulated artemisinin-based combination therapy (ACT). Artemether-lumefantrine has proved effective (cure rates, Ͼ97%) and safe in adults and children in trials conducted throughout the areas of the world affected by malaria (2,13,15,20,23,35,43,44,59). There is a reluctance to prescribe new drugs to pregnant women, and there have been concerns over the safety of artemisinin derivatives in early pregnancy. The curr...

show abstract

Pharmacokinetics of quinine and its metabolites in pregnant Sudanese women with uncomplicated Plasmodium falciparum malaria

Abstract: There was no significant difference in quinine metabolism between pregnant and non-pregnant women and there is no need to adjust quinine dose when treating pregnant women.

Cited by 32 publications

References 28 publications

Pregnancy-Associated Changes in Pharmacokinetics: A Systematic Review

Pregnancy-Associated Changes in Pharmacokinetics: A Systematic Review

Population Pharmacokinetic and Pharmacodynamic Modeling of Amodiaquine and Desethylamodiaquine in Women with Plasmodium vivax Malaria during and after Pregnancy

Population Pharmacokinetics of Lumefantrine in Pregnant Women Treated with Artemether-Lumefantrine for Uncomplicated Plasmodium falciparum Malaria

Contact Info

Product

Resources

About