WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Tacrolimus trough concentration is being currently used for dose individualization.• Limited sampling strategies (LSS) have been developed and validated for renal transplant patients.• Earlier literature has suggested that measurement of tacrolimus AUC is more reliable than trough with respect to both rejection and nephrotoxicity. WHAT THIS STUDY ADDS• Four thousand renal transplants take place annually in India, with many patients prescribed tacrolimus in combination with mycophenolate and steroid.• In this study a LSS with two points, i.e. trough and 1.5 h postdose was developed and validated to estimate AUC0-12.• The added benefit of only a single additional sample with completion of blood collection in 1.5 h and minimum additional cost makes this a viable LSS algorithm in renal transplant patients.• In patients having tacrolimus trough concentrations outside the recommended range (<3 and >10 ng ml -1 in the treatment protocol in our institution) or having side-effects in spite of trough concentrations in the desired range, we can estimate AUC using this LSS for a better prediction of exposure. AIMSTo develop and validate limited sampling strategy (LSS) equations to estimate area under the curve (AUC0-12) in renal transplant patients. METHODSTwenty-nine renal transplant patients (3-6 months post transplant) who were at steady state with respect to tacrolimus kinetics were included in this study. The blood samples starting with the predose (trough) and collected at fixed time points for 12 h were analysed by microparticle enzyme immunoassay. Linear regression analysis estimated the correlations of tacrolimus concentrations at different sampling time points with the total measured AUC0-12. By applying multiple stepwise linear regression analysis, LSS equations with acceptable correlation coefficients (R 2 ), bias and precision were identified. The predictive performance of these models was validated by the jackknife technique. RESULTSThree models were identified, all with R 2 Ն 0.907. Two point models included one with trough (C0) and 1.5 h postdose (C1.5), another with trough and 4 h postdose. Increasing the number of sampling time points to more than two increased R 2 marginally (0.951 to 0.990). After jackknife validation, the two sampling time point (trough and 1.5 h postdose) model accurately predicted AUC0-12. Regression coefficient R 2 = 0.951, intraclass correlation = 0.976, bias [95% confidence interval (CI)] 0.53% (-2.63, 3.69) and precision (95% CI) 6. 35% (4.36, 8.35). CONCLUSIONThe two-point LSS equation .C0) + (3.33.C1.5)] can be used as a predictable and accurate measure of AUC0-12 in stable renal transplant patients prescribed prednisolone and mycophenolate.

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Cyclin-dependent kinase 5 (CDK-5) appears to play a significant role in peripheral nerve regeneration as CDK-5 inhibition retards nerve regeneration following nerve crush. Anti-inflammatory drug acetyl salicylic acid elevates CDK-5 and reduces ischemia – reperfusion injury in cultured neurons. In this study we have evaluated the effect of acetyl salicylic acid on functional recovery following sciatic nerve crush in mice. Eighteen Swiss albino mice underwent unilateral sciatic nerve crush. Test animals received acetyl salicylic acid (100 mg/kg/day, n = 6 or 50 mg/kg/day, n = 6) and control animals (n = 6) received normal saline for 14 days following surgery. Functional recovery was assessed with improvement in Sciatic Function Index, nociception and gait. In comparison with normal saline treatment, acetyl salicylic acid (100 mg/kg/day) significantly improved functional recovery following sciatic nerve crush. Anti-inflammatory drug acetyl salicylic acid appears to be a promising agent for treating peripheral nerve injuries and hence elucidation of its neuroprotective pathways is necessary.

Study design: Prospective, randomized, double-blind clinical trial. Objectives: To evaluate the efficacy of topical phenytoin solution in treating pressure ulcers among patients with spinal cord disorders and to evaluate the systemic absorption of topical phenytoin. Setting: Physical Medicine and Rehabilitation Unit, Christian Medical College, Vellore, India. Methods: Twenty-eight patients with stage 2 pressure ulcers were randomized to receive either phenytoin solution (5 mg/ml) or normal saline dressing on their ulcers once daily for 15 days. Efficacy of the treatment was determined by assessing the reduction in Pressure Ulcer Scores for Healing (PUSH 3.0), ulcer volume and ulcer size as on day 16. Serum phenytoin concentrations were estimated to determine the systemic absorption of topical phenytoin. Results: Statistically insignificant but marginally higher reduction in PUSH 3.0 scores and ulcer size were seen with topical phenytoin treatment. Systemic absorption of topical phenytoin was negligible. No adverse drug events were detected during the study. Conclusions: Phenytoin solution is a safe topical agent that accelerates healing of pressure ulcers. However, its efficacy is only slightly more than normal saline treatment.