RESUMO
OBJECTIVE: To compare the plasma pharmacokinetics of didanosine during once daily (qd) and twice daily (bid) dosing. DESIGN: Open-label, randomized, cross-over study. METHODS: HIV-1 infected patients who used didanosine were randomized to either a qd or a bid dosing regimen of didanosine. The total daily dose of didanosine was identical in both regimens. Seven days after the start of the study, the pharmacokinetic profile of didanosine in plasma and urine was assessed during an 8-h period. The next day, the patient was switched to the opposite dosing regimen, and after another 7 days, the study was concluded by again assessing the plasma and urine pharmacokinetics of didanosine during 8 h. RESULTS: A total of 19 patients completed the study. The pharmacokinetics of didanosine in plasma (with maximum plasma concentration adjusted for dose) and urine were not significantly different in the qd and bid dosing regimen (P > 0.28 for all parameters). CONCLUSION: We conclude that qd dosing of didanosine leads to a similar exposure in plasma as bid dosing (using the same total daily dose). Since qd dosing may lead to improved compliance of patients to regimens containing didanosine, these results provide a rationale for prescribing didanosine in a qd regimen, and is reassuring when we realize that the drug is being administered in a qd dosing regimen on a large scale in clinical practice.
Assuntos
Didanosina/farmacocinética , Infecções por HIV/tratamento farmacológico , HIV-1 , Adulto , Estudos Cross-Over , Didanosina/sangue , Didanosina/química , Didanosina/urina , Esquema de Medicação , Feminino , Infecções por HIV/sangue , Infecções por HIV/urina , Humanos , Masculino , Pessoa de Meia-Idade , Estrutura MolecularRESUMO
Recently, the authors were confronted with interference of stavudine and co-trimoxazole when analyzing the antiretroviral drug didanosine (ddI) in plasma of HIV-1-infected patients using reverse-phase high-performance liquid chromatography with ultraviolet detection. After increasing the percentage of methanol in the mobile phase from 4% to 8% vol/vol and after decreasing the pH of the mobile phase from 6.8 to 5.8, the authors were able to separate didanosine from stavudine and co-trimoxazole (both are frequently used drugs in combination with didanosine). Subsequently, the adapted bioanalytic methodology was validated, and validation results showed that this new methodology can be used for the quantitative determination of didanosine in human plasma. This observation makes clear that combination therapy for human immunodeficiency virus with multiple (often chemically related) drugs has the potential of unexpectedly complicating bioanalytic analyses because therapeutic strategies may change rapidly after publication of a bioanalytic methodology. Thus, it is evident that the investigation of interference of potentially coadministered drugs should be a standard procedure during the development of any bioanalytical methodology in any laboratory.
Assuntos
Fármacos Anti-HIV/sangue , Cromatografia Líquida de Alta Pressão/métodos , Didanosina/sangue , Estavudina/química , Combinação Trimetoprima e Sulfametoxazol/química , Didanosina/química , Didanosina/uso terapêutico , Monitoramento de Medicamentos , Quimioterapia Combinada , Humanos , Plasma/química , Reprodutibilidade dos Testes , Estavudina/uso terapêutico , Combinação Trimetoprima e Sulfametoxazol/uso terapêuticoRESUMO
A high-performance liquid chromatographic method for the quantitative determination of the HIV reverse transcriptase inhibitor lamivudine ((-)-2'-deoxy-3'-thiacytidine, 3TC, Epivir) in human plasma, saliva and cerebrospinal fluid is described. Lamivudine was extracted from samples using silica extraction columns prior to reversed-phase high-performance liquid chromatography with ultraviolet detection at 270 nm. The method has been validated over the range of 10 (lower limit of quantitation) to 5000 ng/ml using a 0.5-ml sample volume. Between-day and within-day precisions ranged from 3.5 to 9.0%. The assay has been used for the quantitative analysis of lamivudine in plasma and cerebrospinal fluid of HIV-1 infected patients.
Assuntos
Fármacos Anti-HIV/análise , Lamivudina/análise , Inibidores da Transcriptase Reversa/análise , Fármacos Anti-HIV/sangue , Fármacos Anti-HIV/líquido cefalorraquidiano , Fármacos Anti-HIV/farmacocinética , Cromatografia Líquida de Alta Pressão , Infecções por HIV/sangue , HIV-1 , Humanos , Lamivudina/sangue , Lamivudina/líquido cefalorraquidiano , Lamivudina/farmacocinética , Reprodutibilidade dos Testes , Inibidores da Transcriptase Reversa/sangue , Inibidores da Transcriptase Reversa/líquido cefalorraquidiano , Inibidores da Transcriptase Reversa/farmacocinética , Saliva/química , Saliva/virologia , Sensibilidade e Especificidade , Espectrofotometria Ultravioleta , Toxoplasmose Cerebral/líquido cefalorraquidiano , Toxoplasmose Cerebral/tratamento farmacológicoRESUMO
A simple, ion-pair high-performance liquid chromatographic method has been developed and validated for the quantitative determination of the HIV protease inhibitor ritonavir in human plasma, cerebrospinal fluid and saliva. Sample pretreatment consisted of precipitation of proteins with acetonitrile prior to high-performance liquid chromatography with ultraviolet detection at 239 nm. The method has been validated over the range of 50 ng/ml to 50 microg/ml with use of 100-microl volumes of sample. The currently described assay has been used successfully for the analysis of ritonavir in plasma, cerebrospinal fluid and saliva in HIV-1 infected patients.