Cytochrome P and the response to antimalarial drugs. The search included only articles published in Spanish, English, and Portuguese on or before 30 June that dealt with only four antimalarial drugs: amodiaquine, chloroquine, mefloquine, and proguanil. RESULTS: Some genetic factors linked to human cytochrome P mainly its polymorphism , as well as other biological and social factors the presence of disease itself, or of inflammation and infection, the use of antimalarials in their various combinations, and the patient's nutritional status influence the behavior of this complex enzymatic system. It has only been in the last decade that the genetics of the cytochromes has been explored and that the mechanisms underlying some therapeutic interactions and aspects of drug metabolism have been uncovered, making it possible to characterize the biotransformation pathway of amodiaquine and chloroquine.
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Cytochrome P and the response to antimalarial drugs. The search included only articles published in Spanish, English, and Portuguese on or before 30 June that dealt with only four antimalarial drugs: amodiaquine, chloroquine, mefloquine, and proguanil.
RESULTS: Some genetic factors linked to human cytochrome P mainly its polymorphism , as well as other biological and social factors the presence of disease itself, or of inflammation and infection, the use of antimalarials in their various combinations, and the patient's nutritional status influence the behavior of this complex enzymatic system.
It has only been in the last decade that the genetics of the cytochromes has been explored and that the mechanisms underlying some therapeutic interactions and aspects of drug metabolism have been uncovered, making it possible to characterize the biotransformation pathway of amodiaquine and chloroquine.
Hopefully new research will help answer the questions that still remain, some of which pertain to the metabolism of other antimalarial drugs, the distribution in the population of the genetic alleles linked to the enzymes involved in their metabolism, the contribution of these genetic mutations to therapeutic failure, and the possibility of predicting the response to antimalarial therapy.
Attention should be given to biological and social factors, such as diet, nutritional status, and inflammatory and infectious processes that are often present in areas where malaria is endemic. Key words: Cytochrome P enzyme system, Plasmodium falciparum, malaria, antimalarials. La nomenclatura de las enzimas depende de la familia, la subfamilia y el gen que las codifica.
En cuanto a su metabolismo, la MQ se transforma en carboximefloquina, que se excreta principalmente con las heces y en menor cantidad por la orina En el estudio de Kaneko et al. Factores que modifican la actividad del CYP Se ha detectado su ARNm en todos los adultos estudiados hasta este momento, aunque no se conoce de un alelo null para el gen CYP3A4 La malaria causada por P. La experiencia en el empleo de diferentes combinaciones de medicamentos ha permitido llegar a algunas conclusiones:.
Efectos del estado nutricional. El consumo de carbohidratos influye en el metabolismo oxidativo de varios medicamentos y su deficiencia reduce la actividad del CYP El presente estudio tiene algunas limitaciones. Washington, D. The use of antimalarial drugs. Report of a WHO informal consultation. Geneva: WHO; Rev Epid Antioq. Rev Panam Salud Publica. Bloland PB. Drug resistance in malaria.
Chamblee, Georgia: World Health Organization; Predictors of mefloquine treatment failure: a prospective study of patients with un-complicated falciparum malaria. Risk factors of chloroquine resistance in Plasmodium falciparum malaria.
Acta Trop. Predictors of treatment failure in multiple drug-resistant falciparum malaria: results from a day follow-up of patients in eastern Thailand. Am J Trop Med Hyg. Chloroquine-resistant Plasmodium falciparum malaria in Ilorin, Nigeria: prevalence and risk factors for treatment failure.
Afr J Med Med Sci. Plasmodium falciparum gametocytaemia in Nigerian children: Peripheral immature gametocytaemia as an indicator of a poor response to chloroquine treatment, and its relationship to molecular determinants of chloroquine resistance. Ann Trop Med Parasitol. Hillier K. Drug interaction with oral contraceptives. Fertil Contracept. Genetic contribution to variable human CYP3A-mediated metabolism. Adv Drug Deliv Rev. Werck-Reichhart D, Feyereisen R.
Cytochromes P a success story. Genome Biol. Pharmacokinetic interactions of antimalarial agents. Clin Pharmacokinet. Identification of human cytochrome P s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data.
Eur J Clin Pharmacol. Characterization of chloroquine plasma protein binding in man. Br J Clin Pharmacol. Drug Metab Dispos. Amodiaquine clearance and its metabolism to N-desethylamodiaquine is mediated by CYP2C8: a new high affinity and turnover enzyme-specific probe substrate. J Pharmacol Exp Ther. Krishna S, White NJ. Pharmacokinetics of quinine, chloroquine and amodiaquine. Clinical implications. Karbwang J, Na-Bangchang K. Clinical application of mefloquine pharmacokinetics in the treatment of P.
Fundam Clin Pharmacol. Acta Pharmacol Sin. Steady-state kinetics of proguanil and its active metabolite, cycloguanil, in man.
Single dose disposition of chloroquine in kwashiorkor and normal children: evidence for decreased absorption in kwashiorkor. Tulpule A, Krishnaswamy K. Chloroquine kinetics in the undernourished. Role of cytochrome P 3A in the metabolism of mefloquine in human and animal hepatocytes.
Life Sci. Cutler DJ. Possible mechanisms of action of antimalarials in rheumatic disease. Agents Actions Suppl. Therapeutic efficacy of sulfadoxine-pyrimethamine, amodiaquine and the sulfadoxine-pyrimethamineamodiaquine combination against uncomplicated Plasmodium falciparum malaria in young children in Cameroon.
Bull World Health Organ. El Bagre, Antioquia, Rev Epidem Antioquia. Wernsdorfer WH. Epidemiology of drug resistance in malaria.
Serious adverse events of mefloquine in relation to blood level and gender. Comparison of adverse events associated with use of mefloquine and combination of chloroquine and proguanil as antimalarial prophylaxis: postal and telephone survey of travellers. Br Med J. Atovaquone and proguanil for Plasmodium falciparum malaria.
The metabolism of chloroquine in man during and after repeated oral dosage. Chloroquine excretion following malaria prophylaxis. Pharmacokinetics of chloroquine in renal insufficiency.
The disposition of chloroquine in healthy Nigerians after single intravenous and oral doses. Influence of route of administration on the pharmaco-kinetics of chloroquine and desethylchloroquine. Bioavailability of hydroxychloroquine tablets in healthy volunteers. The pharmacokinetics of chloroquine in healthy Thai subjects and patients with Plasmodium vivax malaria. The disposition of amodiaquine in man after oral administration. Pharmacokinetics of mefloquine when given as a single and two divided-dose regimens.
Int J Clin Pharmacol Res. Multiple-dose pharmacokinetic study of proguanil and cycloguanil following hourly administration of mg proguanil hydrochloride. Trop Med Parasitol. Parenteral chloroquine for treating falciparum malaria. J Infect Dis. The disposition of amodiaquine in Zambians and Nigerians with malaria.
Population pharmacokinetics of mefloquine in patients with acute falciparum malaria. Clin Pharmacol Ther. Molecular basis of in vivo resistance to sulfadoxinepyrimethamine in African adult patients infected with Plasmodium falciparum malaria parasites. Antimicrob Agents Chemother. Intrinsic efficacy of proguanil against falciparum and vivax malaria independent of the metabolite cycloguanil.
CYP2C8 polymorphism frequencies among malaria patients in Zanzibar.
Hypolipidemic agents drug interactions: approach to establish and assess its clinical significance. Structured review. Franco 1,4 , Y. Henao 1 , M. Monsalve 1,4 , F. Amariles 1,2,4. Universidad de Antioquia.
Intoxicación por antagonistas del calcio