A limited sampling strategy for tacrolimus in renal transplant patients.

AIMS: To develop and validate limited sampling strategy (LSS) equations to estimate area under the curve (AUC(0-12)) in renal transplant patients. METHODS: Twenty-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 AUC(0-12). 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. RESULTS: Three models were identified, all with R(2) > or = 0.907. Two point models included one with trough (C(0)) and 1.5 h postdose (C(1.5)), 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 AUC(0-12). 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). CONCLUSION: The two-point LSS equation [AUC(0-12) = 19.16 + (6.75.C(0)) + (3.33.C1.5)] can be used as a predictable and accurate measure of AUC(0-12) in stable renal transplant patients prescribed prednisolone and mycophenolate.

In vitro Antidiabetic Activity of Polar and Nonpolar Solvent Extracts from Leucas aspera (Willd.) Link Leaves.

BACKGROUND: Diabetes mellitus is a chronic illness, and the management of diabetes is a global problem. Successful treatment is required to prevent complications and organ damages. Herbal medicines are having minimal adverse effects when compared to the available synthetic drugs to treat such chronic diseases and disorders. OBJECTIVE: The present study was aimed to evaluate the antidiabetic and antioxidant activity of polar and nonpolar solvent extracts of Leucas aspera (Willd.) link leaves under in vitro models. MATERIALS AND METHODS: The in vitro antidiabetic activity of petroleum ether (nonpolar) and ethanol (polar) extracts were evaluated in C2C12 cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (cell viability method) and glucose uptake assay. 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging method used for the evaluation of in vitro antioxidant activity. RESULTS: Both the polar and nonpolar solvent extracts of L. aspera had shown better antioxidant activity compared to standard (IC50 = 18.96 and 19.90 µg/mL, respectively). Petroleum ether extract exhibited better cytotoxic activity in C2C12 cell line compared to ethanol extract (concentration of test drug needed to inhibit cell growth by 50% 110.75 ± 5.5 vs. 415.25 ± 8.0 µg/mL) whereas ethanol extract showed enhanced glucose uptake activity than petroleum ether extract in C2C12 cell line at same concentrations. CONCLUSION: From our study results, we concluded that L. aspera (Willd.) link leaves had shown better antidiabetic activity and antioxidant activity under in vitro models. Nonpolar solvent extract produced slightly better activity than polar solvent extract. This study warrants further research and experiments on animal models. SUMMARY: Petroleum ether extract of Leucas aspera (PELA) exhibited slightly higher 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging activity compared to ethanol extract of L. aspera (EELA)PELA exhibited better cytotoxic activity in C2C12 cell line compared to EELAEELA had shown enhanced glucose uptake activity than PELA in C2C12 cell line at same concentrationsL. aspera leaf extracts have potential scavenging of DPPH radicals similar to that of ascorbic acidOverall, PELA (nonpolar) produced slightly better antidiabetic activity and antioxidant activity than EELA (polar). Abbreviations Used: DM: Diabetes mellitus, EELA: Ethanol extract of Leucas aspera, L. aspera: Leucas aspera, PELA: Petroleum ether extract of Leucas aspera.

Case Report of Salmonella gallinarum Urinary Tract Infection in a Renal Allograft Recipient.

Urinary tract infections (UTIs) caused by nontyphoidal Salmonella in a renal allograft recipient are a rare occurrence. Although there is some existing literature on Salmonella typhi bacteriuria and non-typhoidal bacteriuria, none of the cases has been reported in a renal transplant patient. This case report describes a rare instance in which group D Salmonella was isolated from a renal allograft recipient's urine culture and the patient was successfully treated with antibiotics.

Mycophenolic acid area under the curve recovery time following rifampicin withdrawal.

Renal transplant patients prescribed mycophenolate mofetil (MMF) may require treatment for tuberculosis with a regimen including the tuberculocidal drug rifampicin. MMF is an ester prodrug which is rapidly hydrolysed to the active compound, mycophenolic acid (MPA). Therapeutic drug monitoring of mycophenolate involves the measurement of MPA area under the curve (MPA-AUC(0-12)). Rifampicin is known to increase the metabolism and decrease enterohepatic recirculation of mycophenolic acid, (MPA). When MPA is monitored after the discontinuation of rifampicin, an important factor is the time required for the MPA area under the curve to return to the pre-rifampicin value. At present this is not known. This report describes one such renal allograft patient, on long term MMF and prescribed rifampicin by a local physician. As expected there was a clinically significant decrease in MPA-AUC(0-12) Three weeks after rifampicin was discontinued the MPA-AUC(0-12) was still only 65% of the pre-rifampicin value and only 55% of the steady state MPA-AUC(0-12) measured six months later.