P-glycoprotein-dependent pharmacokinetics of irinotecan and its active metabolite, SN-38 in rats: Effect of verapamil

We have recently demonstrated that the oral bioavailability of irinotecan (80 mg/kg) can be increased at least 7-fold by co-administration of the P-gp blocker verapamil (25 mg/kg, Oral). As a result, co-treatment with P-gp inhibitor could be a useful strategy for bioavailability enhancement. However, in view of narrow therapeutic index, the co-administration of irinotecan and verapamil may result in unanticipated toxicities. Therefore, dose optimisation studies of irinotecan were performed when it is given in conjunction with a P-gp inhibitor. For dose optimization study, the bioavailability and pharmacokinetic parameters were studied in rats after oral administration of irinotecan at three doses (i.e. 20, 40 and 80 mg/kg) alone and in combination with verapamil (25 mg/kg, oral). The area under the plasma-concentration time curve (AUC) of irinotecan at 20, 40 and 80 mg/kg was 3.51 ± 1.20, 8.81 ± 1.93 and 14.03 ± 2.18 h µg/ml, respectively which after treatment with verapamil, increased dose dependently to 7.84 ± 1.20, 19.94 ± 2.39 and 61.71 ± 15.0 h µg/ml, respectively. In addition to irinotecan, plasma concentrations of SN-38, one of the major active metabolite of irinotecan, were also monitored. The less than proportional increase in SN-38 AUC from 20 to 80 mg/kg is consistent with the saturation of carboxylesterase. Our results indicate that oral drug treatment of irinotecan in presence of temporary P-gp inhibition could be as equally safe and effective as intravenous administration. Nevertheless, safe P-gp inhibitors need to be identified as alternatives to verapamil for development of efficacious oral irinotecan formulations

Compendious Review on Bioactive Constituents and Pharmacotherapeutic Profile of Heliotropium indicum Linn

: Heliotropium indicum Linn. (syn. Tiaridium indicum) is a widespread plant that grows like a weed and is commonly termed as ‘Hatisundu’ (Family: Heliotropiaceae, Subfamily: Boraginaceae). The plant is endogenous to Southern America and has been naturalized in North America, Africa, Asia and Australia. It is utilized worldwide owing to its ethnomedical significance. The folklore uses of the plant include uterine stimulant, antifertility, diuretic agent and many more. The widespread literature studies reveal that the plant possesses varied pharmacological activities including antimicrobial, antinociceptive, anti-ulcer, anti-glaucoma, anti-tuberculosis, and anti-plasmodial and wound healing. The wild occurrence of this species worldwide provides an opportunity to utilize this plant to paramount levels in treating diverse ailments. This review attempts to provide a comprehensive account of phytochemicals present in the different parts of the plant which are in turn responsible for its therapeutic potential. </jats:sec

To Study the Clinical Profile and Management of Cellulitis of Lower Limb in Northern India

Cellulitis is a bacterial infection of the dermis and subcutaneous tissues occupying a large proportion of hospital beds. This study was conducted for analysis of patients with cellulitis according to their demographics and clinical presentation and to examine their comorbidities, complications, and its management. This observational cross-sectional study was conducted in the Department of Surgery at Santosh Medical College and Hospitals involving a total of 60 cases having cellulitis and other soft tissue infections of lower limb. Analysis of their demographic profile, management, and complications was done. Cellulitis is seen commonly in males, 46 (76.6%). The mean age of patients affected by cellulitis in the study was 36.4 ± 1.23 years. The most common site affected is leg involving more people in field jobs. The most common risk factor was trauma in 46.6%, and other factors were diabetes mellitus and smoking, while abscess formation was the most common complication observed in 36.6% of cases. A total of 56.6% cases were managed conservatively, while 43.3% cases required surgical intervention. Mean hospital stay in this study was 5.02 ± 0.23 days. It was concluded that cellulitis is subcutaneous, spreading bacterial infection is more common in males, and its incidence is highest in working age group population. Lower limb is commonly involved. Trauma, smoking, and diabetes are significant risk factors for development of cellulitis. Abscess is the most common complication. About 50% patients with cellulitis can be managed conservatively and the rest require surgical intervention. </jats:p