Nobuhiro Yasuno

Development and clinical application of high performance liquid chromatography for the simultaneous determination of plasma levels of theophylline and its metabolites without interference from caffeine

A high performance liquid chromatography (HPLC) method has been developed for the simultaneous determination of plasma levels of theophylline and its metabolites without interference from caffeine or caffeine metabolites. The method is simple and of practical use because it is applicable even to plasma samples from patients who take caffeine-containing beverages. The method was also reproducible with a coefficient of variation of less than 5% for each analyte. The levels of theophylline, determined by HPLC, were validated by their high correlation to the levels obtained by fluorescence polarization immunoassay. HPLC was used to determine theophylline levels in patients with bronchial asthma. The data revealed that the ratio of 1,3-dimethyluric acid, the major metabolite of theophylline, to theophylline concentration in the plasma was within a narrow range in most patients (0.055 +/- 0.01, n = 66), regardless of the method of theophylline administration or the time of blood sampling. Conversely, this ratio was as low as 0.027 +/- 0.005 in the patient with a long plasma half-life of theophylline. These results suggest that it may be possible to predict the plasma half-life of theophylline for each patient from a single blood sample. This may be useful when planning theophylline administration, especially in patients with abnormal theophylline metabolism.

Proposal of a Pharmacokinetically Optimized Dosage Regimen of Antibiotics in Patients Receiving Continuous Hemodiafiltration

ABSTRACT The aim of the study was to quantitatively predict the clearance of three antibiotics, amikacin, vancomycin, and teicoplanin, during continuous hemodiafiltration (CHDF) and to propose their optimal dosage in patients receiving CHDF. For this goal, in vitro CHDF experiments with a polyacrylonitrile (PAN) membrane were first performed using these antibiotics, and then the clearances were compared with in vivo CHDF situations determined in 16 critically ill patients. The in vitro CHDF clearances were described as the product of the outflow rate of a drain (Qoutflow) and the drug unbound fraction in artificial plasma, indicating that drug adsorption to the PAN membrane has minor effect on drug clearance in our settings. The observed in vivo clearances also agreed very well with the predicted values, with a product of Qoutflow and plasma unbound fraction, when residual creatinine clearance (CLCR) was taken into account (within a range of 0.67- to 1.5-fold for 15 of 16 patients). Based on these results, a nomogram of the optimized dosages of amikacin, vancomycin, and teicoplanin was proposed, and it was evident that Qoutflow and residual CLCR are major determinants of the dosage and dosing interval for these antibiotics. Although the applicability needs to be confirmed with another type of membrane or higher Qoutflow, our nomogram can help determine the dosage setting in critically ill patients receiving CHDF.

Drug Information to Outpatients Focused on the Initial Signs of Severe Adverse Effects.

We have started to offer drug information to patients with a focus on the initial signs of severe adverse effects. We classified the adverse effects into groups according to the regions of occurrence and edited the initial signs of each group into a compact form to ensure that only the minimum essential information was given out.