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Pharmacokinetic assessment of cefpodoxime proxetil in diabetic rats

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Abstract

Purpose

In diabetes, multi-organ level dysfunction arising from metabolic complications is reported to influence the pharmacokinetics (PK) profile of many drugs. Hence, the present study was planned in rats to evaluate the effect of diabetes on the PK profile of cefpodoxime, a widely prescribed oral antibiotic.

Method

PK profile of cefpodoxime was assessed after oral administration of cefpodoxime proxetil (10 and 20 mg/kg) and intravenous (i.v) administration of cefpodoxime sodium (10 mg/kg) in normal and streptozotocin induced diabetic rats. To evaluate the impact of diabetes on oral absorption and serum protein binding, in situ intestinal permeability and in vitro serum protein binding studies were performed for cefpodoxime using Single Pass Intestinal Perfusion model (SPIP) and ultracentrifugation technique, respectively.

Result

In diabetic rats, there was significant (p < 0.01) decrease in maximum concentration (Cmax) and area under the curve (AUC) of cefpodoxime by both oral and intravenous route, which was attributed to augmented clearance of cefpodoxime. There was no change in the time to achieve Cmax (Tmax) suggesting no alteration in oral absorption which was further confirmed through unaltered intestinal permeability in diabetic rats. The protein binding in diabetic rats also remained unchanged, indicating no influence of protein binding on elevated clearance.

Conclusion

The plasma exposure of cefpodoxime, a renally eliminated drug was significantly lowered in diabetic rats due to enhanced glomerular filtration. However, this observation needs to be confirmed through well controlled clinical trials.

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Acknowledgements

We thank the Wockhardt Research Centre, India and Dr. Mahesh Patel for granting permission for performing these studies.

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Authors and Affiliations

  1. Department of Pharmacy, Panipat Institute of Engineering and Technology, Panipat, Haryana, India

    Garima Mittal & Deepak Prabhakar Bhagwat

  2. Amar Shaheed Baba Ajit Singh Jujhar Singh Memorial College of Pharmacy, Ropar, Punjab, India

    Priyanka Jakhar

  3. Wockhardt Research Centre, Chikalthana, Aurangabad, Maharashtra, India

    Anasuya Patel

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  1. Garima Mittal
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  2. Priyanka Jakhar
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  3. Anasuya Patel
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  4. Deepak Prabhakar Bhagwat
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Contributions

Anasuya Patel and Deepak Prabhakar Bhagwat conceived and designed the research. Garima Mittal and Priyanka Jakhar conducted the experiments and analyzed the data. Garima Mittal wrote the manuscript. All authors approved the manuscript and all data were generated in-house and the authors stated that no paper mill was used.

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Correspondence to Garima Mittal.

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These study protocols were approved by the Institutional animal ethics committee of Wockhardt Research Centre, India registered under Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), India.

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Mittal, G., Jakhar, P., Patel, A. et al. Pharmacokinetic assessment of cefpodoxime proxetil in diabetic rats. J Diabetes Metab Disord 22, 385–392 (2023). https://doi.org/10.1007/s40200-022-01156-3

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  • DOI: https://doi.org/10.1007/s40200-022-01156-3

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