Population pharmacokinetics of steady-state carbamazepine in Egyptian epilepsy patients.

WHAT IS KNOWN AND OBJECTIVE: Individualization of carbamazepine (CBZ) dosage regimen in patients with epilepsy based on based on therapeutic drug monitoring (TDM) followed by estimation of pharmacokinetic (PK) parameters can help in better control of epilepsy. Our objective was to establish a population (POP) PK model of CBZ for Egyptian adult and pediatric patients with epilepsy. METHOD: Single steady-state (SS) trough plasma concentrations of CBZ were available for 302 patients with epilepsy (55·6% men and 44·4% women) who were categorized as children (n = 118) and adults (n = 184) with mean age (years) ± SD of 10·6 ± 4·8 and 29·4 ± 9·9, respectively. Carbamazepine was given as an oral suspension (n = 19) or controlled release tablet (n = 283) with average dose of 15·0 ± 7·8 mg/kg per day. A one-compartment model with first-order absorption and elimination for SS conditions (ADVAN2, SS2, TRANS2) was applied using NONMEM 6.2. Separate absorption rate constants were modelled for the two formulations. The mean POP CL, its intersubject variability (ISV), as well as residual error of CBZ concentration were estimated. RESULTS AND DISCUSSION: The POP estimate for CL was 3·5 L/h with coefficient of variation value of 2·6%, which was consistent with literature data. The ISV on CL was 44·5%. The POP PK model was validated by bootstrap re-sampling, and the individual estimates were within the 95% CI of the bootstrap results. Different covariates that might affect CBZ CL have been evaluated but the limited number of samples per individual prevented precise covariate analysis. WHAT IS NEW AND CONCLUSION: The POP PK model we have developed for CBZ shows good predictive performance in Egyptian adult and pediatric patients with epilepsy. Another PK study to better define the effect of different covariates would improve on the model for dosage individualization.

Aminoglycoside and vancomycin serum concentration monitoring and mortality due to neonatal sepsis in Saudi Arabia.

OBJECTIVE: To assess the effectiveness of monitoring of serum concentration of aminoglycosides in neonates. METHOD: A retrospective evaluation of serum concentration monitoring of aminoglycosides (gentamicin and amikacin) and vancomycin in neonates treated for sepsis in a maternity and children hospital in Jeddah, Saudi Arabia, over the period 1998-2000. RESULTS: The total number of requests for monitoring increased sixfold in 1999 and 12-fold in 2000 relative to 1998. For aminoglycosides, the incidence of both subtherapeutic peak and toxic trough serum levels decreased significantly (P < 0.05) in 1999 and 2000 compared with 1998. Furthermore, the rate of neonatal mortality caused by sepsis showed reduction in both 1999 (34%) and 2000 (35%) in comparison with 1998 (45%). Vancomycin trough (effective) concentration monitoring revealed no change in the incidence (30%) of levels at subtherapeutic values (<5.0 microg/mL) between the compared years. Furthermore, the rate of toxic levels (>10 microg/mL) increased in both 1999 (31%) and 2000 (39%) relative to 1998 (25%). CONCLUSION: Therapeutic drug monitoring of vancomycin needs re-evaluation in the hospital to explain why existing methods are ineffective.

Assessment of liver function by the MEGX test in patients with schistosomiasis and cirrhosis.

OBJECTIVES: The aim of this study was to determine the effect of schistosomiasis infection on hepatic function in Egyptian patients with posthepatitic cirrhosis. DESIGN AND METHODS: Hepatic function, was assessed in 66 Egyptian patients, with (n = 30) and without (n = 36) schistosomal liver fibrosis due to Schistosoma mansoni and in 20 healthy controls, using the monoethylglycinexylidide (MEGX) test. Serum MEGX concentrations were measured before and 5, 15, 30, 60, 120, and 180 min after a lidocaine bolus. The sero-prevalence of antibodies to hepatitis C was also determined in the patients. RESULTS: MEGX test results were significantly lower in patients than in controls at all time points. MEGX test results declined with advancing Child Class. Receiver operating characteristic (ROC) curve analysis revealed the following areas under the ROC curves for discrimination of Child Class C from Child Classes A/B: 30 min, 0.762; 60 min, 0.743; 120 min, 0.731; 15 min, 0.728; 180 min, 0.728; 5 min, 0.602. Schistosomiasis infection had no influence on MEGX test results when cirrhotic patients with (Schisto+) and without (Schisto-) schistosomiasis were compared. While the prevalence of the hepatitis B surface antigen was only 16.7% (Schisto-) and 26.7% (Schisto+), there was an extremely high sero-prevalence of antibodies to hepatitis C (HCV) in both groups: 88.9% (Schisto-) and 73.3% (Schisto+). CONCLUSIONS: The association of schistosomal liver fibrosis with cirrhosis does not additionally influence MEGX formation. In addition, HCV rather than schistosomiasis infection must be considered as a major cause for the progressive liver disease in these patients.