Pharmacokinetics of cefpodoxime proxetil with special reference to biochemical parameters, tissue residue, and spermatozoa motility in rats.

Background : Cefpodoxime is a semisynthetic third generation cephalosporin analogue with a relatively broader spectrum of antimicrobial activity against gram negative and gram positive organisms. This is attributed to their somewhat increased resistance to degradation by the betalactamase. Cefpodoxime shows good activity against Klebsiella pneumonia, many members of enterobactericeae and almost all strains of Escherichia coli. It is extensively used in human beings against infections caused by susceptible organisms for a prolonged period and even without its judicious indication. Though various researchers have worked on the pharmacokinetic aspects of the drug, its effects on biochemical parameters and spermatozoa activity are scarcely available in literature. Aim : To determine the oral kinetic ( blood and tissue) after single therapeutic dose of cefpodoxime proxetil (20mg/kg oral bid 7 days) in rats of either sex on tissue half life and certain biochemical parameters such as glucose, hemoglobin, protein, ALT, AST and other parameters like tissue residue, sperm count and spermatozoa motility in male rats. Materials and Methods : For kinetic studies,24 Wister rats of either sex, 3 months of age, (180-210 gm) were used.(Group I-IV; n=6) Blood samples collected from each animal of Group IV through heart puncture at 0 hour to serve as predrug control. All the group (I-IV) received cefpodoxime proxetil 20 mg/kg once orally as a single dose. At the end of 1,4,12 and 24 hour post oral administration, GroupI,II,III and IVwere utilized for kinetic studies. Blood samples were collected from each animal and vital organs viz brain, lung, liver, spleen, kidney and heart were dissected out for drug analysis and determination of weight. For biochemical parameters, tissue residue and spermatozoa motility, twelve male rats were randomly divided into Groups A and B (n=6) Group B received cefpodoxime (20mg/kg orally bid 7 days) while Group A served as control. Biochemical parameters [Blood glucose, protein, Aspartate transaminase(AST), Alanine transaminase(ALT)and hemoglobin] were measured at 0 and 7 th day while sperm count (total,live and dead)and mean organ weight (study and control group) and tissue residue of drug were evaluated at the end of treatment. Absorption of cefpodoxime was observed at 2 hour and reached a maximum at 4 hour and persisted in blood till 24 hour. Elimination half life in lung was highest followed by heart, liver, kidney and spleen while t½ k in plasma was very low suggesting more affinity of cefpodoxime for tissues than blood. Results and Conclusion : Blood glucose, protein, AST and ALT activities were not significantly altered but the hemoglobin level and total and live sperm count decreased significantly in the study group compared to the control group. Residual level of cefpodoxime was highest in liver followed by kidney and other study organs. Therefore, the drug should be used in human beings judiciously and further study on human subjects is warranted.

Formulation development and Theological studies of palatable cefetamet pivoxil hydrochloride dry powder suspension

Because of its intense bitter taste and susceptibility to moisture Cefetamet Pivoxil [CPH] is presently available only in the form of tablet. The aim of this study was to develop taste masked CPH dry powder suspension. Methods employed for formulations were: a] Film coating of CPH using Eudragit El00 and subsequent adsorption on different carriers such as spray-dried lactose, sodium starch glycolate and spray-dried mannitol and b] Complexation of CPH with three different ion exchange resins indion 234 amberlite IRP64 and amberlite IRP69. Taste viz evaluation as recognized by volunteers revealed that coating with Eudragit El00 and subsequent adsorption on different carriers do not mask the bitter taste of the drug. Suspensions prepared using amberlite IRP64 and amberlite IRP69 were extremely palatable with no bitter after taste. They showed pseudoplastic flow behavior and were too viscous even after shearing for sufficient duration of time and exhibited poor pourability. The suspension made with indion 234 was palatable with slight or no bitter after taste. It demonstrated plastic flow with negligible thixotropy. It had moderate viscosity at rest and could be poured after a reasonable amount of shaking. CPH dry powder suspensions were very unstable under different conditions except under refrigeration. A 5% degradation of drug was occurred in reconstituted suspension in 4 days period when stored at room temperature. Dry powder suspension prepared with indion 234 having 5% overages was stable even after 4th day of reconstitution and palatable with slight or no bitter after taste