Coadministration of rifampicin with fluconazole caused significant changes in the pharmacokinetic parameters of fluconazole. Long-term monitoring for recurrence rates of cryptococcal meningitis is required to assess the clinical significance of this interaction.

An imbalance of oxidative-antioxidant defence mechanism has been proposed in systemic lupus erythematosus patients. Co-administration of N-acetylcysteine (NAC) which has a strong antioxidant activity may produce a satisfactory therapeutic outcome when added to standard therapy. We report a case of a 46-year-old lupus nephritis patient who received 1800 mg of NAC orally. After NAC, this patient showed a higher glutathione level, and a normal level of malondialdehyde, a lipid peroxidation product. In addition, the urinary protein levels, the complete blood counts and physical examination of the affected organs showed improvement. However, a well-controlled trial is needed to confirm the value of high-dose NAC in lupus nephritis patients.

Tamoxifen is a pharmacological estrogen inhibitor that binds to the estrogen receptor (ER) in breast cells. However, it shows an estrogenic effect in other organs, which causes adverse drug reactions (ADRs). The sulfotransferase 1A1 (SULT1A1) enzyme encoded by the SULT1A1 gene is involved in estrogen metabolism. Previous research has suggested that the SULT1A1 copy number is linked with the plasma estradiol (E2) concentration. Here, a total of 34 premenopausal breast cancer patients, selected from the Thai Tamoxifen (TTAM) Project, were screened for their SULT1A1 copy number, plasma E2 concentration and ADRs. The mean age was 44.3 ± 11.1 years, and they were subtyped as ER+/ progesterone receptor (PR)+ (28 patients), ER+/ PR-(5 patients) and ER-/PR-(1 patient). Three patients reported ADRs, which were irregular menstruation (2 patients) and vaginal discharge (1 patient). Most (33) patients had two SULT1A1 copies, with one patient having three copies. The median plasma E2 concentration was 1,575.6 (IQR 865.4) pg/ml. Patients with ADRs had significantly higher plasma E2 concentrations than those patients without ADRs (p = 0.014). The plasma E2 concentration was numerically higher in the patient with three SULT1A1 copies, but this lacked statistical significance.

The aims of this study were to define the relationship between total and unbound valproic acid (VPA) concentrations, to compare pharmacokinetic parameters of total and unbound VPA, and to determine the difference in pharmacokinetic parameters between the seizure-controlled and -uncontrolled groups. Total and unbound steady-state serum concentration of VPA were determined at trough and at 5 hours after the morning dose from 29 pediatric patients with epilepsy who were receiving valproic acid as monotherapy every 8 or 12 hours. Pharmacokinetic parameters were calculated and compared by t test (alpha=0.05). A strong relationship between total and unbound concentrations was found. The equation for predicting unbound concentration from total concentration was unbound concentration=-6.01+0.18 * total concentration (r=0.78, P<0.001). A higher percentage of free fraction was found at higher concentrations. There were significant differences between total and unbound VPA pharmacokinetic parameters. Both the elimination rate constant (Ke) and volume of distribution (Vd) of the unbound VPA were much higher than those of the total VPA; clearance (CI) was approximately 10-fold higher. The seizure-uncontrolled group could eliminate VPA much faster than the seizure-controlled group, as indicated by a much higher Ke and a much shorter t1/2 (P<0.05). Vd of the unbound VPA was also much smaller in the seizure-uncontrolled group (P<0.05). There were significant differences in pharmacokinetic parameters between seizure- controlled and -uncontrolled pediatric epileptic patients. Further study with a larger sample size is strongly recommended.

SUMMARY: Pharmacokinetic studies were performed in 10 stable kidney transplantation patients who received microemulsion formulation (Neoral®) of cyclosporine A (CsA) twice daily. No agents having pharmacokinetic effects on CsA had been used in these patients. The values of various basic pharmacokinetic parameters were similar to those reported in Western literature. The complete area under the blood concentration–time curve (AUC) of CsA for the duration of 12 h (12‐h AUC) was determined using the linear trapezoidal rule from seven concentrations at 0, 1, 2, 4, 6, 8, and 12 h after CsA administration. The mean values of 12‐h AUC were 4603.63 ± 344.61 ng h/mL. CsA concentrations at 2 h after dosing (not the trough levels) showed the best correlation with the complete AUC (r2 = 0.9322). The abbreviated AUC of CsA was calculated either by stepwise multiple linear regression analysis or by the linear trapezoidal rule from a few sampling time points. Using stepwise multiple linear regression analysis, which was used in calculating abbreviated AUC in all previous studies, the model equation that had the highest correlation and the lowest prediction error with the complete AUC was derived by using CsA concentrations at 2 and 8 h after dosing (12‐h AUC = 4.262C2 + 8.390C8− 669.417; r2 = 0.9808, absolute prediction error = 3.97 ± 0.96). Two model equations derived using the linear trapezoidal rule provided the best correlation with the complete AUC: (1) The two time points selected model equation 12‐h AUC = 4C2 + 5C8; r2 = 0.9780, absolute prediction error = 6.41 ± 1.22). (2) The three time points selected model equation 12‐h AUC = 4C0 + 3C2 + 5C6; r2 = 0.9475, absolute prediction error = 5.00 ± 1.41). When different pharmacokinetic data sets were applied to the model equations derived using regression analysis, the values of coefficients and the constant of the regression equation had changed from the initial equation. Thus, new model equations will emerge every time the new data are applied. In contrast, the values of coefficients in the model equation calculated using trapezoidal rule were unaltered when tested by the new pharmacokinetic data set. Thus, the abbreviated AUC derived using the linear trapezoidal rule would be simpler than and superior to that obtained using stepwise multiple linear regression analysis in prediction of the complete AUC.