Pharmacokinetic study of mycophenolic acid in Iranian kidney transplant patients

The purpose of this study was to characterize the pharmacokinetic parameters of mycophenolic acid [MPA] in Iranian kidney transplant patients. Plasma MPA concentration of mycophenolate mofetile [MMF] 1 gram two times a day was measured in 21 Iranian kidney transplant recipients receiving treatment. Patients who entered the study had been transplanted for more than 3 months and their drug level was supposed to be at steady state. MMF concentration was measured with High- Performance Liquid Chromatography [HPLC]. The plasma MPA concentration-time curve was characterized by an early sharp peak at about 1 hour postdose. The mean Area Under Curve [AUC], Cmax and Tmax were 47.0 +/- 18.3 microg.h/ml, 18.6 +/- 8.5 microg/ml and 1.0 +/- 0.5 hours respectively. The plasma MPA concentration-time curve pattern of Iranian patients was similar and consistent with previously reported profiles in other populations taking the same dose.

effect of prednisolone on the sensitivity of Technetium 99m-methylene diphosphonate [[99m] Tc-MDP] scintigraphy to detect simulated closed fracture in the rat tibia

The purpose of the present study was to evaluate the effect of prednisolone on the sensitivity of bone scanning to detect the simulated closed fracture in the rat tibia. A total number of forty eight adult, male NMRI rats randomly assigned into two parts, one part for 4 and other for 8 weeks experiments. Each part has been divided into four groups, one group not receiving prednisolone [control group] and the other groups receiving 5, 10 and 20 mg/kg prednisolone respectively. After four and eight weeks of experiments a simulated closed fracture was created in the tibia approximately 1 cm near knee joint. .The scintigraphy imaging has been performed on second and fifth day after tibial bone fracture and the ratio of the activity of tibia bone fracture to the contra lateral healthy side was calculated [R factor]. All scintigraphy images showed the rat tibia bone fracture. Statistically significant difference in the R factors have been observed, when scintigraphy images were performed in fifth day after injury. Bone radionuclide scanning by [99m]Tc-MDP is very sensitive for detection of occult fracture. In order to enhance bone scan sensitivity, it may be reasonable to postpone [99m]Tc-MDP scintigraphy imaging at least 2 to 3 days after suspected trauma in patients receiving glucocorticoid medication

evaluation of the possible effect of positive end expiratory pressure [PEEP] on pharmacokinetics of phenytoin in patients with acute brain injury under mechanical ventilation

Positive ventilation has shown to have an influence on pharmacokinetic and disposition of some drugs.Beacause phenytoin with a narrow therapautic range, is the most commonly used drug for prophylaxis and treatment of early seizures after acute brain injuries, in the present study the effect of short term PEEP [5-10 cm H2O for at least 8 hours] on phenytoin serum concentration and pharmacokinetic parameters such as Vmax and clearance in brain injured patients under mechanical ventilation was examined. Ten patients with moderate to severe acute brain injury who were placed on mechanical ventilation with an initial PEEP level of 0-5 cm H2O were included in the study. Patients received phenytoin loading dose of 15 mg/kg followed by a maintenance daily dose of 3-7 mg/kg initiated within 12 hours of loading dose. Sampels were taken on two different occasions before and after PEEP elevation. Total phenytoin serum concentrations were determined by HPLC method. A time invarient Michaelis-Menten pharmacokinetic model was used to calculate Vmax and clearance for each patient.Derrived variables were calculated as follows: Vmax, 3.5-6.8 and 3.7-8.2 mg/kg/day; Clearance, 0.1-0.7 and 0.1-1.2 l/kg/day [before and after PEEP elevation, respectively]. Our data have shown a wide range of variability [2.6-32.5 mg/l] in phenytoin serum concentrations. There were no statistically significant differences in the measured total concentrations [p=0.721] and calculated Vmax and clearance [p=0.285]before and after PEEP elevation. Administration of fluid and inotropic agents, limitation in application of higher levels of PEEP and drug interactions, shall be considered as possible explanations for these findings