The daily dose of ribavirin is currently determined based on body weight. In the present study, the authors examined factors influencing total plasma clearance (CL(total)) and the toxic level on red blood cells of ribavirin in such body weight-based dosage adjustment in Japanese chronic hepatitis C patients (13 male and 6 female). Patients received ribavirin (600 or 800 mg/d) orally, depending on their body weights, together with interferon alpha-2b (6 million units) intramuscularly. A steady-state trough plasma concentration (C(pss)) was achieved approximately 4 weeks after the initiation of treatment, but the value was scattered among patients in a range from 1100 to 4200 ng/mL. The high C(pss) of ribavirin of approximately 4000 ng/mL decreased hemoglobin concentrations to less than 8.5 g/dL. The individual CL(total), estimated by dividing dose normalized by body weight by C(pss), of ribavirin correlated significantly with the patient's creatinine clearance. In contrast, no relationship was observed with other parameters such as age, body weight, serum creatinine concentration, alanine aminotransferase (ALT) concentration, or aspartate aminotransferase (AST) concentration, though ALT and AST concentrations decreased with ribavirin treatment in most patients. These results indicate that CL(total) of ribavirin is dependent on renal function (creatinine clearance), and hemolysis is induced by high ribavirin concentrations in plasma. Dosage adjustment of ribavirin based on renal function and body weight would provide effective and safer treatment without causing hemolysis.
When patients received H2RA or PPI, the laxative effect of MgO is decreased possibly due to the low solubility of MgO at the higher gastric pH and less generation of MgCl2 and Mg(HCO3)2. Higher dosing level of MgO or another laxative should be used in patients taking H2RA or PPI, as well as the case of patients with total gastric resection.
A drug interaction derived from the displacement of lidocaine from tissue binding sites by mexiletine that resulted in the increased plasma lidocaine concentrations was shown. This observation had implications for loading doses and acute effects of lidocaine in the concurrent therapy of lidocaine and mexiletine.
Propofol is a comparatively new intravenous anesthetic drug. We measured the concentration of propofol in the plasma of both the arterial blood and the venous blood using highperformance liquid chromatography (HPLC) in 12 patients who underwent propofol anesthesia. The pharmacokinetic behavior of propofol concentration in the venous blood was similar to that in the arterial blood. Both concentrations reflected the pharmacological effects based on the changes in several monitoring values (blood pressure, the pulse, Sjo 2, SEP). The monitoring of intravenous anesthetic drugs are done using arterial blood. Using this method we can therefore easily monitor propofol which is recently being used for sedation by collecting venous blood samples.
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