Clinical Pharmacology

Pharmacodynamic

The primary mechanism of action of Ofloxacin appears to be the specific inhibition of DNA gyrase (topoisomerase II). This enzyme is responsible for the negative super coiling of the bacterial DNA and consequently for its topological configuration, governing functions such as RNA transcription, protein synthesis, DNA replication and repair functions. The nitro group in ornidazole is reduced to more reactive amine that attacks the microbial DNA that brings about loss of helical structure of DNA and subsequent DNA breakage.

The antibacterial and antiprotozoal activity of Mebatic is due to synergistic effect of Ofloxacin, Ornidazole. Mebatic acts by inhibiting DNA gyrase, a type II topoisomerase and topoisomerase IV, which is an enzyme necessary to separate replicated DNA, thereby inhibiting cell division also interferes with DNA replication by inhibiting an enzyme complex called DNA gyrase.

Pharmacokinetics

Plasma half life of Ofloxacin is 9 hours in Mebatic after infusion and elimination is mainly by renal excretion. The half life of Ornidazole is about 13 hours. Eighty five (85%) of a single dose is eliminated within the first 5 days, most of this being metabolized. 4% of the dose is excreted as unaltered substance in the urine. Ornidazole is mainly metabolized to 2-hydroxymethly and a-hydroxymethyl derivatives in the liver. Both main metabolites are less active against Trichomonas vaginalis and anaerobic bacteria than the unchanged ornidazole.

The mean volume of distribution after IV administration is 1 liter/kg. Plasma protein binding of ornidazole is about 13%. Mebatic IV penetrates the cerbospinal fluid, the body fluid and the tissues such as testis, brain, ovary, uterus, lungs and intestine very effectively. Plasma concentration are within the range considered to be optimal for the various indications. After repeated administration of 1400mg or more every 12 hours to healthy volunteers drug accumulation was observed.

Mebatic Clinical Trial Data

A comparative study was conducted on 200 subjects (Arm A: 100 subjects were treated with Mebatic, Arm B: 50 subjects were treated with Ofloxacin, alone and Arm C: 50 subjects were treated with Metronidazole alone) to evaluate efficacy and safety of the fixed dose combination of Ofloxacin Ornidazole (Mebatic) with Ofloxacin and Metronidazole, alone treatment in mixed dysentry, acute appendicitis, upper respiratory tract infections, acute pelvic inflammations diseases and septic abortion.

Table: efficacy of Mebatic and Ofloxacin multicenteric randomized compiled results of Phase III clinical trials
Disease Conditions Therapy Used No. of patient enrolled No. of patients completely cured on 7th day of treatment No. of patients not completely cured on 7th day of treatment % curability
Mixed Dysentery Mebatic 54 50 4 92.6
Ofloxacin 9 6 3 66.7
Metronidazole 6 4 2 66.7
Acute Appendicitis Mebatic 13 11 2 84.6
Ofloxacin 6 3 3 50
Metronidazole 31 20 11 64.5
Upper respiratory Infections Mebatic 11 10 1 90.9
Ofloxacin 6 3 3 50
Metronidazole 4 2 2 50
Acute Pelvic Inflammatory Diseases Mebatic 10 8 2 80
Ofloxacin 7 4 3 57.1
Metronidazole 7 4 3 57.1
Septic Abortion Mebatic 12 10 2 83.3
Ofloxacin 22 15 7 68.2
Metronidazole 2 1 1 50