title: [Lack of bioavailability of generic lopinavir/ritonavir not prequalified by WHO marketed in Africa (Congo Brazzaville)].
abstract: Although second-line generic antiretroviral drugs are of great value in developing countries there are concerns regarding their quality and safety. This study is a case report and pharmacological study in healthy volunteers. A French subject of sub-saharan origin who visited Republic of Congo received a post-exposure treatment with AZT+3TC and LPV/r (200/50 mg, Arga-L®, India) following unprotected sexual intercourse. Two days later, in France, tests showed that plasma concentrations of lopinavir and ritonavir were undetectable. The WHO prequalification list showed Arga-L® was not prequalified. A pharmacological study in healthy volunteers evaluated oral bioavailability: plasma concentrations of generic LPV/r Arga-L® and LPV/r Kaletra® (400/100 mg) were measured after one single dose at 7 days apart in four healthy volunteers. Concentrations of Arga-L® at 12 h after intake were considerably lower than those of Kaletra®, revealing very low oral bioavailability of generic lopinavir and ritonavir (<10%) compared to the brand-name drug. We found that Arga-L®, despite having adequate qualitative and quantitative drug contents, had very poor bio availability compared to Kaletra®. In order to avoid the selection and the spread of drug-resistant HIV strains, rigorous pharmacological monitoring of generic antiretroviral drugs that are not pre-qualified by WHO, but are marketed in Africa, must be a priority for health authorities.
authors.affiliation: Hôpital Foch, 40 rue Worth, 92151, Suresnes cedex, France. lseydouc@yahoo.fr.
authors.forename: S
authors.initials: S
authors.lastname: Camara
authors.affiliation: Hôpital Foch, 40 rue Worth, 92151, Suresnes cedex, France.
authors.forename: D
authors.initials: D
authors.lastname: Zucman
authors.affiliation: Hôpital Foch, 40 rue Worth, 92151, Suresnes cedex, France.
authors.forename: M
authors.initials: M
authors.lastname: Vasse
authors.affiliation: France Expertise Internationale, 1, quai de Grenelle, 75015, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Goudjo
authors.affiliation: Solthis, 58A, rue du Dessous des Berges, 75013, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Guillard
authors.affiliation: Hôpital Bichat-Claude Bernard laboratoire pharmaco-toxicologie, 46 rue Henri Huchard, 75877, Paris cedex 18, France.
authors.forename: G
authors.initials: G
authors.lastname: Peytavin
mesh_terms: D000349:Africa; D003132:Commerce; D003223:Congo; D003906:Developing Countries; D017277:Drug Approval / Q000191:economics; D004338:Drug Combinations; D016568:Drugs, Generic / Q000191:economics / Q000627:therapeutic use*; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D015497:HIV-1; D006801:Humans; D061466:Lopinavir / Q000097:blood / Q000191:economics / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019438:Ritonavir / Q000097:blood / Q000191:economics / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013810:Therapeutic Equivalency; D014944:World Health Organization
chemical_list: D004338:Drug Combinations; D016568:Drugs, Generic; C558899:lopinavir-ritonavir drug combination; D061466:Lopinavir; D019438:Ritonavir
keywords: Bio-equivalence; Congo Brazzaville; Developing countries; France; Generic Drugs; HIV; Hospital; Pharmacokinetic Studies; Ritonavir; Sub-Saharan Africa; WHO; lopinavir