Reduced Plasma Concentrations of Antituberculosis Drugs in Patients with HIV Infection

Sahai, Jan; Gallicano, Keith; Swick, L; Tailor, Sandra A.N.; Garber, Gary; Seguin, Isabelle; Oliveras, Laia; Walker, Susan Noble; Rachlis, A.; Dw, Cameron

doi:10.7326/0003-4819-127-4-199708150-00006

Cited by 154 publications

(123 citation statements)

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“…However, this study demonstrated that the bioavailability of RMP in HIV-infected patients with and without TB was decreased, as evidenced by a significant reduction in peak concentration and exposure. Similar findings have been reported by Sahai et al (17), who conducted a pharmacokinetic study of Canadian subjects with HIV infection. Low concentrations of RMP in blood could be due to malabsorption of the drug (2).…”

supporting

confidence: 77%

“…However, patients with advanced human immunodeficiency virus (HIV) disease with or without diarrhea may not adequately absorb anti-TB drugs (3,(13)(14)(15). Also, the degrees of malabsorption appear to differ across populations (4,6,17,19). We recently observed that HIV-infected patients with and without TB had malabsorption of rifampin (RMP) and isoniazid (INH), as determined on the basis of the urinary excretion of the drugs (7).…”

mentioning

confidence: 99%

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Decreased Bioavailability of Rifampin and Other Antituberculosis Drugs in Patients with Advanced Human Immunodeficiency Virus Disease

Gurumurthy

Ramachandran

Kumar

et al. 2004

Antimicrob Agents Chemother

136

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We evaluated the effects of human immunodeficiency virus (HIV) disease on pharmacokinetics of antituberculosis medications by measuring concentrations of isoniazid and rifampin in blood and of pyrazinamide and ethambutol in urine. Peak concentration and exposure were reduced for rifampin, and rapid acetylators of isoniazid had lower drug levels. HIV and HIV-tuberculosis patients who have diarrhea and cryptosporidial infection exhibit decreased bioavailability of antituberculosis drugs

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supporting

confidence: 77%

mentioning

confidence: 99%

Decreased Bioavailability of Rifampin and Other Antituberculosis Drugs in Patients with Advanced Human Immunodeficiency Virus Disease

Gurumurthy

Ramachandran

Kumar

et al. 2004

Antimicrob Agents Chemother

136

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“…For humans without tuberculosis who received a single 250-mg oral dose of isoniazid, elimination half-lives have been reported to be 1.2 and 3.3 h in fast and slow acetylators, respectively, and peak concentrations in plasma (at 1 h postdosing) have been reported to be 2.44 and 3.64 g/ml, respectively (25). Several investigators in the United States have reported that the absorption of antimycobacterial agents is impaired in patients with AIDS (18,27,29 . However, this effect was not demonstrated in Kenyan patients, in whom concentrations in plasma were not different among individuals with or without AIDS or with or without diarrhea (9).…”

mentioning

confidence: 99%

Effects of Gender, AIDS, and Acetylator Status on Intrapulmonary Concentrations of Isoniazid

Conte

Golden

McQuitty

et al. 2002

Antimicrob Agents Chemother

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The objective of the present study was to evaluate the effects of gender, AIDS, and acetylator status on the steady-state concentrations of orally administered isoniazid in plasma and lungs. Isoniazid was administered at 300 mg once daily for 5 days to 80 adult volunteers. Subjects were assigned to eight blocks according to gender, presence or absence of AIDS, and acetylator status. Blood was obtained prior to administration of the first dose, 1 h after administration of the last dose, and at the completion of bronchoscopy and bronchoalveolar lavage (BAL), which was performed 4 h after administration of the last dose. The metabolism of caffeine was used to determine acetylator status. Standardized bronchoscopy was performed without systemic sedation. The volume of epithelial lining fluid (ELF) recovered was calculated by the urea dilution method. Isoniazid concentrations in plasma, BAL fluid, and alveolar cells (ACs) were measured by high-performance liquid chromatography. AIDS status or gender had no significant effect on the concentrations of isoniazid in plasma at 1 or 4 h. Concentrations in plasma at 4 h and concentrations in ELF were greater in slow acetylators than fast acetylators. The concentration in plasma (1.85 ؎ 1.60 g/ml [mean ؎ standard deviation; n ‫؍‬ 80]) at 1 h following administration of the last dose was not significantly different from that in ELF (2.25 ؎ 3.50 g/ml) or ACs (2.61 ؎ 5.01 g/ml). For the entire study group, concentrations in plasma at 1 h were less than 1.0, 2.0, and 3.0 g/ml for 34.7, 60, and 82.7% of the subjects, respectively; concentrations in ELF were less than 1.0, 2.0, and 3.0 g/ml in 30 (37.5%), 53 (66.0%), and 58 (72.5%) of the subjects, respectively; and concentrations in ACs were less than 1.0, 2.0, and 3.0 g/ml in 43 (53.8%), 59 (73.8%), and 65 (81.3%) of the subjects, respectively. The concentrations of orally administered isoniazid in plasma were not affected by gender or the presence of AIDS. The concentrations in plasma at 4 h and the concentrations in ELF, but not the concentrations in ACs, were significantly greater in slow acetylators than fast acetylators. Concentrations in plasma and lungs were low compared to recommended therapeutic concentrations in plasma and published MICs of isoniazid for Mycobacterium tuberculosis. The optimal concentrations of isoniazid in ACs and ELF are unknown, but these data suggest that the drug enters these compartments by passive diffusion and achieves concentrations similar to those found in plasma.Isoniazid is an essential drug in the treatment of tuberculosis. For humans without tuberculosis who received a single 250-mg oral dose of isoniazid, elimination half-lives have been reported to be 1.2 and 3.3 h in fast and slow acetylators, respectively, and peak concentrations in plasma (at 1 h postdosing) have been reported to be 2.44 and 3.64 g/ml, respectively (25) 1993). However, this effect was not demonstrated in Kenyan patients, in whom concentrations in plasma were not different among individuals with or without AIDS or w...

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“…The extent of reduction of serum carotene is secondary to its oxidation and consequent depletion by singlet oxygen (Bendich, 1993). Circulating concentrations of drugs can also be lower in the HIV-infected than in the HIV-uninfected (Sahai et al, 1997). We chose treatment with a relatively high dose of natural mixed carotenoids in the current trial because of the known absorption defect in AIDS that affects drug and micronutrient concentrations, and because similar doses of carotenoids are safe in short-and long-term use.…”

Section: Mixed Carotenoids In Hiv Infectionmentioning

confidence: 99%

A community randomized controlled clinical trial of mixed carotenoids and micronutrient supplementation of patients with acquired immunodeficiency syndrome

Austin¹,

Singhal

Voigt³

et al. 2006

Eur J Clin Nutr

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Objective: This clinical trial aims to evaluate if natural mixed carotenoids supplementation can improve the health and survival of acquired immunodeficiency syndrome (AIDS) patients. Design: A placebo-controlled, prospective, randomized, double-blind, multicenter clinical trial. Setting: Community, tertiary care human immunodeficiency virus (HIV) clinics of the Canadian HIV Trials Network (CTN). Participants: Three hundred and thirty-one adults with advanced AIDS on conventional management were recruited during routine clinic visits. Interventions: All participants, including 166 controls, received daily oral specially formulated multivitamins including vitamin A and trace elements; 165 treatment group participants received additional daily oral natural mixed carotenoids, equivalent to 120 000 IU (72 mg) of b-carotene daily. Follow-up was quarterly at routine clinic visits. Results: Mean (s.d.) follow-up was for 13 (6) months. Thirty-six participants died by 18 months. Serum carotene concentration o1.0 mmol/l was present in 16% participants at baseline. Despite variation in carotene content of the treatment medication, serum carotene concentrations increased significantly to twice the baseline levels to 18 months follow-up in participants who received carotenoids treatment compared with controls (Po0.0001). Although not statistically significant, mortality was increased in participants who did not receive carotenoids treatment compared with those who did (HR time to death 1.76, 95% CI 0.89, 3.47, P ¼ 0.11). In multivariate analysis, survival was significantly and independently improved in those with higher baseline serum carotene concentrations (P ¼ 0.04) or higher baseline CD4 T-lymphocyte counts (P ¼ 0.005). Adjusted mortality was also significantly and independently increased in those who did not receive carotenoids treatment compared with those who did (HR time to death 3.15, 95% CI 1.10, 8.98, P ¼ 0.03).

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Reduced Plasma Concentrations of Antituberculosis Drugs in Patients with HIV Infection

Abstract: Reduced total drug exposure may be related to malabsorption in persons with HIV infection or AIDS.

Cited by 154 publications

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Decreased Bioavailability of Rifampin and Other Antituberculosis Drugs in Patients with Advanced Human Immunodeficiency Virus Disease

Decreased Bioavailability of Rifampin and Other Antituberculosis Drugs in Patients with Advanced Human Immunodeficiency Virus Disease

Effects of Gender, AIDS, and Acetylator Status on Intrapulmonary Concentrations of Isoniazid

A community randomized controlled clinical trial of mixed carotenoids and micronutrient supplementation of patients with acquired immunodeficiency syndrome

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