Comparison of whole-blood tacrolimus concentrations measured by different immunoassay systems.

INTRODUCTION: Different measured values for tacrolimus were obtained with different automated immunoassays. We aimed to examine the differences in the blood tacrolimus concentrations measured by the major immunoassay systems commercially available in Japan. METHODS: Whole-blood samples from 118 patients were assayed by 3 commercial assays: chemiluminescent enzyme immunoassay (CLIA), affinity column-mediated immunoassay (ACMIA), and enzyme-multiplied immunoassay technique (EMIT). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used for reference. KEY FINDINGS: The correlation coefficient of immunoassay vs LC-MS/MS was excellent for ACMIA (.83) and CLIA (.81) and good for EMIT (.71). The mean error was negative for ACMIA and positive for CLIA and EMIT. The mean absolute error and root-mean-square error were almost the same for ACMIA and CLIA and lower than those for EMIT. CONCLUSIONS: The ACMIA and CLIA yield considerably better results than the EMIT for monitoring blood tacrolimus concentrations.

One-side-coated insert as a unique ophthalmic drug delivery system.

We newly prepared a unique one-side-coated insert that releases drug from only uncoated side. The purpose of this study is to determine whether ocular and systemic absorption of ophthalmic drug could be altered by an inserting direction of the insert in rabbit eyes. One-side-coated insert was prepared by attaching a polypropylene tape on the one side of the polymer disc of poly(2-hydroxypropyl methacrylate) (HPM) containing tilisolol as a model ophthalmic drug. The insert was applied in the lower conjunctival cul-de-sac of albino rabbits with the uncoated side facing bulbar conjunctiva/sclera (SC insert) or palpebral conjunctiva (CJ insert). At the adequate intervals, the tear fluid, plasma, aqueous humor, conjunctiva, and sclera were collected and the drug concentrations were determined by an HPLC. A release of tilisolol from the one-side-coated insert was twice slower than from the uncoated insert. Ocular application of the one-side-coated insert produced the constant concentrations of tilisolol in the tear fluid over 180 min. SC insert showed higher drug concentrations in the aqueous humor and sclera, and lower drug concentrations in the plasma and conjunctiva than CJ insert.The one-side-coated insert can alter the ocular and systemic absorption of drug by an inserting direction.

Effect of nizatidine on paracetamol and its metabolites in human plasma.

The effect of the histamine H2-receptor antagonist, nizatidine, on plasma concentrations of paracetamol has been investigated with respectto hepatic metabolism. Paracetamol (1000 mg) together with 300 or 150 mg nizatidine or placebo was orally administered to five healthy male volunteers. Venous blood samples were taken before and after administration. Plasma paracetamol and paracetamol conjugates (glucuronide and sulfate) were measured by high-performance liquid chromatography. The pharmacokinetic parameters were calculated from the plasma paracetamol concentration-time curves of each volunteer. The plasma nizatidine concentration was highest (2420.0+/-192.4 and 996.0+/-54.6 ng mL(-1)) in the sample taken 1 h after administration of 300 mg nizatidine (high dose) and 150mg nizatidine (low dose), respectively. Plasma paracetamol concentrations with nizatidine (high and low doses) were increased significantly at 45-120 min and 45-60 min, respectively, compared with placebo. The total area under the plasma paracetamol concentration-time curve from 0 to 180 min (2361.5+/-146.4 and 2085.75+/-73.5 microg min mL(-1)) significantly increased after coadministration of nizatidine (high and low doses), respectively (P < 0.01 vs placebo). Paracetamol glucuronide concentrations with nizatidine (high and low doses) were decreased significantly at 30-45 min and 30 min, respectively, compared with placebo. However, plasma paracetamol sulfate concentrations with nizatidine (high and low doses) were not significantly altered. The coadministration of nizatidine (150 and 300 mg) dose-dependently reduces plasma paracetamol glucuronide concentrations and increases plasma paracetamol concentrations. The effects of nizatidine could result from the inhibition of glucuronyltransferase. Thus, care is necessary when paracetamol and nizatidine are coadministered.