Diagnostic efficiency of truncated area under the curve from 0 to 2 h (AUC0₋2) of mycophenolic acid in kidney transplant recipients receiving mycophenolate mofetil and concomitant tacrolimus.

BACKGROUND: Recently, the use of the truncated area under the curve from 0 to 2 h (AUC(0-2)) of mycophenolic acid (MPA) has been proposed for therapeutic monitoring in liver transplant recipients. The aim of our study was the evaluation of the clinical usefulness of truncated AUC(0-2) in kidney transplant patients. METHODS: Plasma MPA was measured in samples taken before the morning dose of mycophenolate mofetil, and one-half and 2 h post-dose, completing 63 MPA concentration-time profiles from 40 adult kidney transplant recipients. The AUC from 0 to 12 h (AUC(0-12)) was calculated using the validated algorithm of Pawinski et al. The truncated AUC(0-2) was calculated using the linear trapezoidal rule, and extrapolated to 0-12 h (trapezoidal extrapolated AUC(0-12)) as previously described. RESULTS: Algorithm calculated and trapezoidal extrapolated AUC(0-12) values showed high correlation (r=0.995) and acceptable dispersion (ma68=0.71 µg·h/mL), median prediction error (6.6%) and median absolute prediction error (12.6%). The truncated AUC(0-2) had acceptable diagnostic efficiency (87%) in the classification of subtherapeutic, therapeutic or supratherapeutic values with respect to AUC(0-12). However, due to the high inter-individual variation of the drug absorption-rate, the dispersion between both pharmacokinetic variables (ma68=6.9 µg·h/mL) was unacceptable. CONCLUSIONS: The substantial dispersion between truncated AUC(0-2) and AUC(0-12) values may be a serious objection for the routine use of MPA AUC(0-2) in clinical practice.

Relation of blood platelet count during carbamazepine and oxcarbazepine treatment with daily dose, and serum concentrations of carbamazepine, carbamazepine-10, 11-epoxide, and 10-hydroxycarbazepine.

BACKGROUND: Carbamazepine (CBZ) occasionally causes haematological disorders such as thrombocytopenia, and recently a case of oxcarbazepine (OXCBZ)-induced thrombocytopenia has been described. The aim of our study was blood platelet count determination in epileptic patients treated with CBZ and OXCBZ, and its relationship with the dose and serum levels of these drugs and its metabolites. METHODS: The serum levels of CBZ and its epoxide, and the pharmacologically active monohydroxy derivative of OXCBZ were determined in 137 patients treated with CBZ, and 60 patients treated with OXCBZ. The platelet count, mean platelet volume, and platelet size distribution width were also determined. RESULTS: The difference between the platelet counts of the patient groups treated with CBZ and OXCBZ was not significant. No significant correlations between the platelet count and serum levels of the administered antiepileptic drugs and their metabolites were found. However, significant negative correlations between the platelet count and the daily doses of CBZ and OXCBZ were obtained (p<0.01). In 5 cases (4 treated with CBZ and 1 with OXCBZ) the platelet count was <150 x 10(9)/l. CONCLUSIONS: In accordance with the mean platelet volume and platelet distribution width, the thrombocytopenia observed in some of the patients studied was due to a hyper-destruction of peripheral blood platelets. However, the results obtained suggest that the mechanism of CBZ or OXCBZ-induced thrombocytopenia is not due to a direct toxicity of these drugs or their major metabolites on the circulating platelets. Although, the patients treated with OXCBZ shown a lower prevalence for thrombocytopenia (1.7%) than those treated with CBZ (2.9%), the routine platelet count monitoring in patients treated with both drugs may be recommended.

A thermodynamic study of beta-N-acetylhexosaminidase enzyme heterogeneity in cerebrospinal fluid from patients with multiple sclerosis.

BACKGROUND: ss-N-acetylhexosaminidase (Hex) is a lysosomal hydrolase, whose determination in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) has provided discordant results. METHODS: Total Hex and its isoenzymes Hex A and Hex B were determined using a thermodynamic procedure in the CSF of 27 patients with definitive MS, 8 with possible MS, 9 with meningitis, 14 with other neurological diseases, and in 10 controls without any neurological disease. RESULTS: In the group of patients with definitive MS, the total Hex and Hex A were significantly higher than in the control group (p<0.001), with a possible association of greater enzymatic activities with the presence of oligoclonal bands and recent relapse; however, an overlap was detected for the activities of total Hex and its isoenzymes between the groups of patients with different neurological diseases. A significant correlation was obtained for neuron-specific enolase (NSE) with total Hex and Hex A and Hex B isoenzymes (p<0.001); however, in the partial correlation statistical significance was only obtained between NSE and Hex A (p<0.001) which is the most abundant Hex isoenzyme in the brain. CONCLUSIONS: Although the inflammatory process in MS mainly takes place in the perivascular zone, with little activity in the cerebral parenchyma, the significant increase of NSE and Hex A isoenzyme in CSF reveals a neuronal damage. The disease status may have effect on the CSF Hex activity.