Placental and Milk Transfer of Chloroquine in Humans

Akintonwa, A; Gbajumo, S. A.; Mabadeje, A. F. B.

doi:10.1097/00007691-198802000-00004

Cited by 46 publications

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“…during the second stage of labour [4].The mean (95% CI) concentrations in mixed cord blood, maternal blood and the C/M ratio were 736 mg l -1 (505, 967), 683 mg l -1 (609, 757) and 0.98 (0.86, 1.1), respectively. In our 19 pregnant women who received a mean dose of 26.3 mg kg -1 significantly earlier (3 months before delivery), there were much lower mean plasma concentrations of both CQ and DECQ in maternal and cord serum, but mean C/M ratios were similar to those of Akintowna et al [4] at 1.1 for CQ and 1.2 for DECQ. These results show that both CQ and its major metabolite DECQ distribute equally across the placenta, suggesting that fetal exposure will be proportional to the maternal dose and its frequency.…”

Section: Discussionmentioning

confidence: 94%

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Transfer of chloroquine and desethylchloroquine across the placenta and into milk in Melanesian mothers

Law

Ilett

Hackett

et al. 2008

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• The literature on placental and milk transfer of chloroquine and its major bioactive metabolite desethylchloroquine is sparse and incomplete. WHAT THIS STUDY ADDS• We have provided data on the transplacental transfer of chloroquine and desethylchloroquine in Melanesian women (n = 19), measured transfer of these drugs into breast milk (n = 16) and estimated absolute and relative infant doses for the breastfed infant.• The data for desethylchloroquine are novel.• In all three areas we have significantly increased both quantity and quality of the available database. AIMSTo investigate the transfer of chloroquine and its major bioactive metabolite desethylchloroquine across the placenta and into breast milk. METHODSIn Papua New Guinea, chloroquine (CQ; 25 mg base kg ) is recommended for prophylaxis of malaria during pregnancy, and at the Alexishafen Health Centre women are routinely prescribed CQ at the time of delivery. Fetal-cord and maternal serum samples were collected at delivery (n = 19) and milk samples were collected from day 3 to day 17-21 after delivery (n = 16). CQ and its primary active metabolite desethylchloroquine (DECQ) were quantified by high-performance liquid chromatography. For both CQ and DECQ cord/maternal ratios (C/M) were calculated to characterize placental transfer, and infant exposure via milk was estimated by standard methods. RESULTSThe median (interquartile range) C/M was 1.1 (0.9, 1.6) for CQ and 1.2 (0.5, 1.8) for DECQ. The average concentration in milk over the time of sampling was 167 mg l -1 (27, 340) for CQ and 54 mg l -1 (22, 106) for DECQ. Estimated absolute and relative infant doses were 34 mg kg -1 day -1 (7, 50) and 15 mg kg -1 day -1 (4, 26), and 2.3% (0.5, 3.6) and 1.0% (0.4, 2.0) for CQ and DECQ (as CQ equivalents), respectively. CONCLUSIONInfant exposure to CQ and DECQ during pregnancy will be similar to that in the maternal circulation, and dependent on maternal dose and frequency. The median CQ + DECQ relative infant dose of 3.2% (as CQ equivalents) was low, confirming that use of CQ during lactation is compatible with breastfeeding.

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Section: Discussionmentioning

confidence: 94%

“…The data quality is also variable because of small subject numbers in each study (1)(2)(3)(4)(5)(6)(7)(8)(9)(10), and wide variability in drug measurements per subject (13)(14)(15)(16)(17). Only three studies used AUC data to estimate milk Cavg.…”

Section: Discussionmentioning

confidence: 99%

Transfer of chloroquine and desethylchloroquine across the placenta and into milk in Melanesian mothers

Law

Ilett

Hackett

et al. 2008

Brit J Clinical Pharma

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“…Different studies have demonstrated that CQ, HCQ and their metabolites are excreted and can be found in breast milk, moreover transplacental passage has been also observed [90,91].…”

Section: Pharmacokinetics and Pharmacodynamics Of Antimalarials: Can mentioning

confidence: 99%

Reappraisal of Antimalarials in Interferonopathies: New Perspectives for Old Drugs

Piscianz

Cuzzoni

Sharma

et al. 2018

CMC

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The story of antimalarials as antinflammatory drugs dates back few centuries. Chinin, the extract of the Cinchona bark, has been exploited since the 18th century for its antimalarial and antifebrile properties. Later, during the Second World War, the broad use of antimalarials allowed arguing their antirheumatic effect on soldiers. Since then, these drugs have been broadly used to treat Systemic Lupus Erythematosus, but, only recently, the molecular mechanisms of action have been partly clarified.The inhibitory action on vacuole function and trafficking has been considered for decades the main mechanism of the action of antimalarials, affecting the activation of phagocytes and dendritic cells. In addition, chloroquine is also as a potent inhibitor of autophagy, providing another possible explanation of its antinflammatory action. However, much attention has been recently devoted to the action of antimalarials on the so-called cGAS-STING pathway deputed to the sensing of nucleic acid and to the production of type 1 interferons. This pathway is a fundamental mechanism for host defence, since it is able to detect microbial DNA and RNA and induce the immune response that will lead to the production of interferons. Of note, genetic defects in disposal of nucleic acids lead to inappropriate activation of the cGAS-STING pathway and inflammation. These disorders, named type I interferonopathies, represent a valuable model to study the antinflammatory potential of antimalarials.We will discuss possible development of antimalarials to improve the treatment of type I interferonopathies and, likely multifactorial disorders characterised by interferon inflammation, such as systemic lupus erythematosus.

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“…The ratio of the concentrations of fetal to maternal blood depends on the chemical structure of the drugs and ranges from 0.33 for cyclosporin A (21) to greater than 1 for chloroquine (22). The rate of transfer, however, is dependent on a variety of factors including molecular size and lipophilicity, degree of ionization and binding to blood components and placental tissue.…”

Section: Transplacental Exposure To Genotoxinsmentioning

confidence: 99%

Transplacental transfer of genotoxins and transplacental carcinogenesis.

Autrup

1993

Environ Health Perspect

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A number of chemical compounds induce cancer in the offspring of animals treated with these compounds. The fetus is sensitive to the toxic and teratogenic effects of chemicals in the early embryonic stages, whereas it is sensitive to carcinogenic effects during late fetal stages. Carcinogens may be direct acting or may require metabolic oxidation such as those in tobacco smoke. Activation can occur in utero. Animal experiments indicate that tumors can be initiated in utero, commonly by activation of cellular proto-oncogenes, and that promotion can occur after birth by postnatal treatment with tumor promoters. This may have important implications for humans. The initial peak of cancer incidence during the first 5 years of life may be due to prenatal exposure of either parent to mutagens, but the role of paternal exposure in relation to childhood cancer is controversial. There is an increased risk of cancer in children whose fathers work in heavy industry or whose mothers work in medical or dental services. The exact etiological agents have not been unequivocally identified. Information on human transplacental exposure to carcinogens and genotoxins is limited and based on measurement of maternal plasma concentrations or analysis of cord blood. Transplacental transfer of carcinogens in smoke and smoke-related damage to fetal tissue have been demonstrated. The mycotoxin aflatoxin B1 or its metabolites have been detected in cord blood, as have metabolites of pesticides and polychlorinated biphenyls. New biomarkers may provide important information on the transplacental transfer of genotoxic compounds.(ABSTRACT TRUNCATED AT 250 WORDS)

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Placental and Milk Transfer of Chloroquine in Humans

Cited by 46 publications

References 0 publications

Transfer of chloroquine and desethylchloroquine across the placenta and into milk in Melanesian mothers

Transfer of chloroquine and desethylchloroquine across the placenta and into milk in Melanesian mothers

Reappraisal of Antimalarials in Interferonopathies: New Perspectives for Old Drugs

Transplacental transfer of genotoxins and transplacental carcinogenesis.

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