Turning intermittent regimens into daily regimens using blister-packs. An exploration in murine tuberculosis.

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.

• 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)

Chemical References

• Antitubercular Agents
• Pyrazinamide
• Ethambutol
• Isoniazid
• Rifampin

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)