Enhanced Oral Bioavailability of Paclitaxel in Presence of P-gp Blockers: Smart Extraction Procedure, Antitumor and Side Effects Study in Mice | ||||
| Azhar International Journal of Pharmaceutical and Medical Sciences | ||||
| Article 11, Volume 2, Issue 1, January 2022, Page 108-116 PDF (606.94 K) | ||||
| Document Type: Original research articles | ||||
| DOI: 10.21608/aijpms.2021.69294.1056 | ||||
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| Authors | ||||
Mona Sakr  1; Moneim Osman2; Magda Ismail 3; Yasmine Attia4
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| 1Department of Pharmacology and Toxicology, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt | ||||
| 2Department of Pharmacology, National Cancer Institute, Cairo, Egypt | ||||
| 3Department of Pharmaceutical Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt | ||||
| 4Department of Pharmacology, National Cancer Institute, Cairo University, Cairo, Egypt. | ||||
| Abstract | ||||
| Paclitaxel is microtubule-stabilizing anticancer drug . Because of its poor bioavailability, the drug is usually given by I.V. infusion, formulated in a mixture of Cremophor EL and ethanol . Oral administration of Paclitaxel would offer several advantages to the patient: avoid the adverse effects caused by Cremophor EL vehicle , medication would no longer require a visit to the out-patient clinic, and it may allow the achievement of lasting therapeutic plasma levels. Oral bioavailability of Paclitaxel may be enhanced by the co-administration of Cyclosporine and Verapamil as P-gp efflux pump blockers. Rh-123, an indirect index of P-gp transport was used to measure the P-gp efflux pump activity in the intestinal wall likes Paclitaxel. . The results showed that dichloromethane (DCM) was the most efficient organic solvent to extract paclitaxel from the plasma samples with a recovery of almost 100%. The oral bioavailability of paclitaxel was enhanced 2.7 fold by verapamil, and up to 5.7 fold by cyclosporine, showing that both drugs effectively inhibited the P-gp pump in the intestinal tract, allowing for better absorption of paclitaxel. Concerning the antitumor activity of Paclitaxel, both Cyclosporine and Verapamil did not adversely affect the antitumor activity of Paclitaxel in tumor-bearing mice, while Cyclosporine showed 4.3 days delay in tumor growth compared to control untreated mice. Additionally, toxicity’s parameters such as leukocytes count, serum level of LDH and CK were investigated to ensure that the enhanced absorption of Paclitaxel does not aggravate its toxicity. | ||||
| Keywords | ||||
| Paclitaxel; extraction; oral bioavailability; P-gp blockers; antitumor; histopathology; toxicity | ||||
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