Rifin Forte Bio availability & Bioequivalence®
Rifin Forte Bio availability & Bioequivalence®
STUDY OBJECTIVES
• To determine the bioavailability of Rifampicin, Isoniazid, Pyrazinamide
& Ethambutol as a single dose in a fixed dose combination formulation,
Rifin Forte relative to that of equivalent doses of reference preparations
of the four drugs. To evaluate the bioequivalence of Rifampicin, Isoniazid,
Pyrazinamide & Ethambutol in the fixed dose combination formulation
by comparison to the reference preparations.
STUDY DESIGN
• A single dose open label, Laboratory blinded 2-way crossover study
in 24 healthy volunteers.
• Study volunteers were drawn from the students and staff at LCPS
and from the residents of the nearby village.
TEST PRODUCT Rifin Forte*
Tablet containing 150mg Rifampicin, 75mg Isoniazid, 400mg Pyrazinamide
and 275mg Ethambutol Hcl
REFERENCE PRODUCTS
• Two fixed dose combination tablets of Rimactal-INH 300 (Biochemie
Pakistan) each containing 300mg Rifampicin and 150mg Isoniazid
• 3 tablets of Pyrazinamide 500 mg (Ciba, Novartis Pakistan; each
tablet containing SOOmgof Pyrazinamide)
• 3 tablets of Myambutol 400mg (Wyeth Pakistan Ltd. each tablet
containing 400mg of Ethambutol)
STUDY
ADMINISTRATION
The study was conducted jointly by the division of Pharmacology, University
of Cape Town, South Africa (a WHO recommended center for assessing
the bio-availability of Rifampicin in FDCs) and the Lahore college of
Pharmaceuticals sciences in Pakistan.
The tuberculosis drug concentrations were analyzed by Validated LC-MS
methods in the division of pharmacology laboratory which is recognized
internationally for this purpose and is ISO 17025 accredited.
RESULTS OF BIOAVAILABILITY STUDY
Parameters in bio-equivalence i.e. time to peak plasma concentration (T
max) and peak Plasma concentration (C max) of Antitubercular formulation.
FDC test drug Rifin Forte'" (Pacific Pakistan) in comparison to equivalent
oral doses of reference formulations Rimactal INH° 300mg tablets (Biochemie,
Pakistan), PZA° SOOmg tablets of (Ciba, Novartis - Pakistan) and Myambutol
400mg Tablets (Wyeth, Pakistan Ltd.) in the fasted state to healthy volunteers
are shown in table 1
| Parameters & Units | Rifampicin | Isoniazid | Pyrazinamide | Ethambutol | ||||
| Test Drug | Ref. Drug |
Test Drug | Ref. Drug |
Test Drug | Ref. Drug |
Test Drug | Ref. Drug |
|
| Mean time to peak plasma Concentration(Tmax) | 2.61 | 2.49 | 1.86 | 1.56 | 2.78 | 1.94 | 3.38 | 3.22 |
| Mean Peak plasma Concentration(Cmax) | 7.60 | 7.89 | 3.43 | 3.56 | 27.53 | 28.05 | 4.47 | 3.88 |
