Excretion of chloroquine and desethylchloroquine in human milk.

Ogunbona, F. A.; Onyeji, Cyprian O.; Bolaji, Oluseye O.; Torimiro, S. E. A.

doi:10.1111/j.1365-2125.1987.tb03078.x

Cited by 36 publications

(18 citation statements)

References 7 publications

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“…In a number of studies, CQ or its metabolites (Edstein et al 1986;Ogunbona et al 1987;Ette et al 1987a, b, c;Akintonwa et al 1988) as well as HCQ have been shown to be excreted in breast milk (Nation et al 1984;Østensen et al 1985). Transplacental transmission of CQ and HCQ has also been observed (Akintonwa et al 1988;CostedoatChalumeau et al 2002).…”

Section: Excretion In Breast Milk and Transplacental Passagementioning

confidence: 89%

Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases

et al. 2015

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HCQ and CQ have a good reputation for being effective and relatively safe treatments in SLE, mild-moderate RA and Sjøgren's syndrome. There is need for (a) more information on their mode of action in relation to the control of these diseases, (b) scope for developing formulations that have improved pharmacokinetic and therapeutic properties and safety, and (c) further exploring their use in drug combinations not only with other disease modifying agents but also with biologics.

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Section: Excretion In Breast Milk and Transplacental Passagementioning

confidence: 89%

Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases

et al. 2015

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“…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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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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“…Following the administration of a single chloroquine 300mg base dosage to lactating women, the milk: plasma ratio in AVCs ranged from approximately 2 to 4,f113] Following single oral doses of chloroquine 600mg, 24 hour milk: plasma concentration ratios approximated 7 for chloroquine and 2 for desethylchloroquine,f1l4] V sing peak milk concentrations and assuming a daily milk ingestion of lL by the infant, the maximum percentage of the maternal dose recovered in milk over 9 days was estimated at 0.7 to 4% of the matemalloading dose,f113. 114] During long term treatment, steady-state chloroquine concentrations may be higher and might expose the infant to higher drug concentrations. After a 5-day treatment totalling 2.1g of chloroquine to a lactating woman, the maximum amount of chloroquine ingested by the infant was estimated at 2 mg/day, which would be insufficient to induce any pharmacological effect.…”

Section: Clinical Pharmacokinetics In Pregnancy and Lactationmentioning

confidence: 99%

Clinical Pharmacokinetics and Metabolism of Chloroquine

Ducharme

Farinotti

1996

Clinical Pharmacokinetics

272

233

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This paper presents the current state of knowledge on chloroquine disposition, with special emphasis on stereoselectivity and microsomal metabolism. In addition, the impact of the patient's physiopathological status and ethnic origin on chloroquine pharmacokinetics is discussed. In humans, chloroquine concentrations decline multiexponentially. The drug is extensively distributed, with a volume of distribution of 200 to 800 L/kg when calculated from plasma concentrations and 200 L/kg when estimated from whole blood data (concentrations being 5 to 10 times higher). Chloroquine is 60% bound to plasma proteins and equally cleared by the kidney and liver. Following administration chloroquine is rapidly dealkylated via cytochrome P450 enzymes (CYP) into the pharmacologically active desethylchloroquine and bisdesethylchloroquine. Desethylchloroquine and bisdesethylchloroquine concentrations reach 40 and 10% of chloroquine concentrations, respectively; both chloroquine and desethylchloroquine concentrations decline slowly, with elimination half-lives of 20 to 60 days. Both parent drug and metabolite can be detected in urine months after a single dose. In vitro and in vivo, chloroquine and desethylchloroquine competitively inhibit CYP2D1/6-mediated reactions. Limited in vitro studies and preliminary data from clinical experiments and observations point to CYP3A and CYP2D6 as the 2 major isoforms affected by or involved in chloroquine metabolism. In vitro efficacy studies did not detect any difference in potency between chloroquine enantiomers but, in vivo in rats, S(+)-chloroquine had a lower dose that elicited 50% of the maximal effect (ED950) than that of R(-)-chloroquine. Stereoselectivity in chloroquine body disposition could be responsible for this discrepancy. Chloroquine binding to plasma proteins is stereoselective, favouring S(+)-chloroquine (67% vs 35% for the R-enantiomer). Hence, unbound plasma concentrations are higher for R(-)-chloroquine. Following separate administration of the individual enantiomers, R(-)-chloroquine reached higher and more sustained blood concentrations. The shorter half-life of S(+)-chloroquine appears secondary to its faster clearance. Blood concentrations of the S(+)-forms of desethylchloroquine always exceeded those of the R(-)-forms, pointing to a preferential metabolism of S(+)-chloroquine.

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Excretion of chloroquine and desethylchloroquine in human milk.

Cited by 36 publications

References 7 publications

Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases

Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases

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

Clinical Pharmacokinetics and Metabolism of Chloroquine

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