Albendazole and its metabolites in the breast milk of lactating women following a single oral dose of albendazole

Albendazole is used in several antihelminthic drug programs. The need may rise to include sectors of the community [like nursing women] not previously involved in community or clinical programs. The problem of the impact of excreted drug and its metabolites in milk on the breast-fed infant is addressed. To study the pharmacokinetic parameters of albendazole and its metabolites in the milk of lactating women one single 400 mg oral dose of albendazole. 33 lactating women [age 18-40] were selected and participated in the study. They all received a single oral 400 rug dose of albendazole. Five milk samples were taken at 0, 6, 12, 24 and 36 hours after the oral dose. One serum sample was taken after 6 hours [with the 2nd milk sample]. Samples were analyzed using HPLC method. Pharmacokinetc study was performed. Albendazole 'AB' and its inactive metabolite ABSN were scarcely detected in milk samples after six hours of the oral dose. Only the active metabolite, ABSX, could be diluted at levels that allows pharmacokinetic study. The pharmacokinetic parameters of albendazole s11p13ide 'ABSX', were calculated as follows: 35 1.91 +/- 32.4 ng/mL; 6.9 +/- 0.49 hs; 12.37 +/- 2.18 hs and 5 190.28 +/- 482.8 ng. hr/mL for Cmax, Tmax, t 1/2 and AUCO-36, respectively. The ratio of albendazole and its metabolite was determined. After an oral dose of 400 rug, AB and ABSX attain levels in milk that are hardly considered harmful for the breast-fed infant

Frequency and risk factors of hepatotoxicity of anti Tuberculous drugs

Hepatotoxicity is reported in patients using first-line anti-tuberculous drugs regimen, among them 6-12% die. Identifying the risk factors for developing hepatotoxicity would probably reduce morbidity and mortality associated with T.B management. To study the frequency and risk factors of hepatotoxic reactions in patients receiving firat-line anti-tuberculous drugs. In addition to determine the relation between acetylator phenotype and anti-tuberculous drug hepatotoxicity. Seventy seven patients consecutively presenting to Suez Chest Hospital with active T.B diseases [WHO criteria], who were eligible for anti- tuberculous regimens [WHO guidelines] were included. Child B or C cirrhotic patients or Child A with liver enzymes exceeding double the normal were excluded in addition patients suffering from chronic renal or cardiac disease, hypersensitivity to anti-tuberculous drugs or receiving potentially hepatotoxic medications for other reasons were also excluded. 1-Rate of hepatotoxic reactions according to the diagnostic criteria. 2- Rates of fast and slow acetylator phenotypes. 3- Rate of risk factors among patients with hepatotoxicity versus patients without hepatotoxicity. Hepatotoxic reactions have been diagnosed in seven [9.1%] patients. By univariate analysis, age over 60 years [p = 0.02], alcoholism [p = 0.02], extra-pulmonary tuberculosis [p = 0.02] and severe forms of tuberculosis [p = 0.03] were statistically significant risk factors. Fifty eight [75.3%] of the study sample were slow acetylators, while 8 [10.4%] were fast acetylators. Three out of the eight [37.5%] of fast acetylators and only [6.9%] of the slow acetylators developed hepatotoxicity [p = 0.03]. Logistic regression models showed that fast acetylator phenotype was the only significant [p = 0.04] risk factor for early hepatotoxicity. Alcoholism [p = 0.01] was a significant risk factor for late hepatotoxicity. Hepatotoxic reactions among patients receiving anti-tuberculous drugs remain a considerable problem. Two patterns of liver injury can be observed. The first occurs earlier and is associated with fast acetylator phenotype. The second occurs later and is associated with alcoholism and HCV infection

Gamma aminobutyric acid [GABA] and glutamate levels in the csf of epileptic children

Thirty-one children divided into 3 groups were studied. Group I included 13 neurologically free children, aged 3-9 years and not receiving any medications. Group II consisted of 7 recently diagnosed non medicated epileptic children, aged 3.5-8 years. Eleven medicated epileptic children; aged 4-9 years represented group III. All children were examined thoroughly. EEG and brain CT scan were done for epileptic children. Gamma Aminobutyric acid [GABA] and Glutamate levels in CSF were assessed for all children by HPLC. The mean CSF levels of GABA were lowest in non-medicated epileptic children. Control of the seizures by anti-epileptic drugs [AEDs] was associated by a concomitant re-increase in the CSF GABA levels. The mean glutamate CSF levels did not differ significantly among the three studied groups. Nevertheless, it was noticed that the GABA / Glutamate ratio was higher in medicated than in non-medicated epileptic children. It could be concluded that CSF GABA levels as well as the GABA / Glutamate ratio can reliably monitor the epileptic control by pharmacotherapy