Abstract | SETTING: Blisterpacks might be used to present low cost intermittent regimens while maintaining an easily remembered daily frequency of opening blisters, by alternating blisters containing 2 of the drugs of a 4-drug regimen with blisters containing the remaining 2 drugs. OBJECTIVE: The efficacy of the alternating regimens was examined in murine tuberculosis. DESIGN: 2 weeks after infection with Mycobacterium tuberculosis H37Rv, groups of mice were treated with rifampicin (R) 15 mg/kg, isoniazid ( H) 25 mg/kg, pyrazinamide ( Z) 300 mg/kg, ethambutol (E) 100 mg/kg three times weekly (RHZE3); RH/ZE, an alternating regimen of RH on days 1, 3 and 5 of the week and ZE on days 2, 4 and 6, RZ/HE or RE/HZ. RESULTS: Spleen and lung bacillary counts at 7 and 12 weeks indicated large differences in the efficacy of the regimens: RZ/HE > RE/HZ > RHZE3 > RH/ZE. Serum assays showed that Rifampicin (RMP) levels were much lower after HRZE and slightly lower after RZ, RE and RH than after R alone, whereas levels were similar when R was given before the remaining drugs; also, the absorption of Z was slightly increased by R. A second experiment used the same 4 regimens but gave R before other drugs. The organ colony forming units counts at 6 and 12 weeks were then similar. A third experiment examined continuation phase regimens of R3, R2, R2H2 and R2H6 given after daily RHZ treatment for 4 weeks. It found R2H2 only slightly superior to R2H6 and R3 much better than R2. CONCLUSION: 1. Alternating initial phase regimens were as effective as conventional intermittent regimens. 2. R3H6 might be an optimal continuation phase regimen for blisterpacks.
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Authors | A Guy, J M Dickinson, D A Mitchison |
Journal | Tubercle and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease
(Tuber Lung Dis)
Vol. 74
Issue 5
Pg. 310-6
(Oct 1993)
ISSN: 0962-8479 [Print] Scotland |
PMID | 8260664
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antitubercular Agents
- Pyrazinamide
- Ethambutol
- Isoniazid
- Rifampin
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Topics |
- Animals
- Antitubercular Agents
(administration & dosage)
- Drug Administration Schedule
- Drug Packaging
- Drug Therapy, Combination
- Ethambutol
(administration & dosage)
- Isoniazid
(administration & dosage)
- Mice
- Mice, Inbred BALB C
- Pyrazinamide
(administration & dosage, blood)
- Rifampin
(administration & dosage, blood)
- Tuberculosis
(blood, drug therapy)
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