Subject(s)
Antipsychotic Agents/adverse effects , Neuroleptic Malignant Syndrome/diagnosis , Neuroleptic Malignant Syndrome/etiology , Risperidone/adverse effects , Adult , Antipsychotic Agents/therapeutic use , Dementia/drug therapy , Diagnosis, Differential , Humans , Male , Risperidone/therapeutic useABSTRACT
Lamivudine has recently been registered for the treatment of chronic hepatitis B patients. The main therapeutic outcome in the studies on which the registration was based was a drop of HBV DNA below 10(7) genome equivalents/ml, the level of detection of the insensitive Abbott Genostics assay. However, as we have reported previously, with the use of sensitive PCR-based assays, individual differences in virological response to lamivudine can be detected. As a first step in analysing the chain of events after oral intake of lamivudine we modified and validated a high-pressure liquid chromatography (HPLC) method to evaluate lamivudine plasma levels. Lamivudine levels in chronic hepatitis B patients who participated in a study on the efficacy of lamivudine were comparable to our reference curve, which was derived from eight chronic hepatitis B patients. From the reference curve, a mean area under the curve (AUC) of 4994 mcg/l.h (SD 1524), a mean t(max) of 42 minutes (SD 11), and a mean C(max) of 1.9 mg/l (SD 0.70) were calculated. Lamivudine exerts its action as the active triphosphate inside the hepatocyte after extensive handling. Therefore, additional steps in the pharmacokinetic process should be evaluated to explore the potential mechanisms that are responsible for the diversity in quantitative HBV DNA response to lamivudine.
Subject(s)
Hepatitis B, Chronic/blood , Hepatitis B, Chronic/drug therapy , Lamivudine/blood , Lamivudine/therapeutic use , Reverse Transcriptase Inhibitors/blood , Reverse Transcriptase Inhibitors/therapeutic use , Adolescent , Adult , Chromatography, High Pressure Liquid , Female , Humans , Lamivudine/pharmacokinetics , Male , Middle Aged , Reverse Transcriptase Inhibitors/pharmacokineticsABSTRACT
The effect of activated charcoal administration on the secretion of theophylline from the blood into the intestinal lumen has been examined by use of the rat isolated vascularly perfused small intestine. A closed two compartment model was used to analyse the vascular and luminal concentration-time curves obtained. An equation was derived to calculate the time-dependent intestinal clearance. From control experiments it was concluded that theophylline is secreted by a diffusional transport system through the intestinal wall. The intestinal clearance declined rapidly with time as a result of the concomitant increase in luminal theophylline concentration. After 120 min a steady state between the vascular and luminal perfusate was established. Administration of activated charcoal in the lumen had a profound effect on the kinetics of the drug. The vascular steady state concentration was depressed dramatically. The theophylline clearance remained nearly constant with time, because the blood to lumen concentration gradient was maximized. The maximal value for the intestinal theophylline clearance was estimated to be 0.88 mL min-1 and it equalled the value for the intestinal blood flow at the absorptive site. By use of the concept of absorptive site blood flow, the maximal effect of charcoal on systemic theophylline clearance could be adequately predicted for rats, dogs and man. Activated charcoal administration is only useful to enhance the systemic clearance of drugs or toxicants if that clearance is of the same order of magnitude as the absorptive site blood flow or lower.
