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J Meinshausen

Publications and source records attributed to J Meinshausen.

4 recordsLinked to original sources
PubMed1993

Generation of pharmacokinetic data during routine therapeutic drug monitoring: Bayesian approach vs. pharmacokinetic studies.

In three groups (each n = 12) of unselected hospitalized patients treated either with digoxin, theophylline, or gentamicin routinely performed TDM measurement of trough steady-state plasma levels (+ peak levels in case of gentamicin) was combined with a pharmacokinetic study at steady state (multiple blood sampling during one dosing interval). Pharmacokinetic parameters (apparent volume of distribution Vd, total plasma clearance CL) needed for individualization of dosage were evaluated by the Bayesian approach and a model-(in)dependent pharmacokinetic program (TOPFIT). Comparison of both methods revealed some small differences in the pharmacokinetic parameters for all three drugs. Mean deviations of the Bayesian estimates from the pharmacokinetic calculations of the three drugs ranged between 20 and 38% for Vd and between 13 and 22% for CL, indicating that the Bayesian approach provided reliable pharmacokinetic estimates for individualizing drug dosage under routine conditions. Therefore, it is suggested that routine TDM combined with Bayesian-based analyses can be regarded as an alternative to pharmacokinetic studies in clinically relevant populations.

Adult↗
PubMed1991

[Therapy-refractory primary intestinal lymphangiectasis].

A 20-year-old man with severe physical weakness (from which he soon recovered spontaneously) was found to have hypoproteinaemia and lymphocytopenia (768/microliters). Ten years later, after having been free of symptoms in the meantime, oedema, ascites and abdominal pain occurred, associated with loss of physical capacity. Enteric loss of protein (alpha 1-antitrypsin clearance increased about thirtyfold) with a total serum protein concentration of only 3.7 g/dl, as well as histological evidence of lymphangiectasia of the small and large intestines provided the diagnosis of primary intestinal lymphangiectasia. In the course of the disease cholelithiasis and (after treatment with tranexamic acid) thrombosis of the axillary vein occurred. No treatment has been of any avail and the patient has been unable to work for three years.

Adult↗
PubMed1990

Is cyclosporin A an inhibitor of drug metabolism?

1. The potential for a drug interaction between cyclosporin A and midazolam was investigated since both compounds appear to be metabolized by the same cytochrome P-450 isoenzyme. 2. In vitro evaluation of the binding of cyclosporin A to rat microsomal cytochrome P-450 indicated a Ks-value of 0.4 microM. In further studies with rat liver microsomes IC50-values of 6, 8 and 70 microM cyclosporin A were determined for the inhibition of the metabolism of midazolam to its alpha-OH-,4-OH- and di-OH-metabolites, respectively. 3. Comparative studies with human liver microsomes indicated IC50-values of approximately 300 microM for the formation of alpha-OH-midazolam and of 65 microM for the formation of 4-OH-midazolam. 4. The pharmacokinetics of a single intravenous dose of midazolam (0.075 mg kg-1) was studied in nine patients receiving cyclosporin A to prevent rejection of their transplanted kidneys. The average steady state blood concentrations of cyclosporin A, measured by r.i.a. using a specific monoclonal antibody, varied during a dosing interval between 175 and 600 ng ml-1. 5. In these patients the hepatic elimination of midazolam was characterized by a mean t1/2 (+/- s.d.) of 2.3 +/- 1.2 h and a plasma clearance (CL) of 414 +/- 95 ml min-1. These values were not different from those of normal human subjects (t1/2 = 1.5 to 4 h, CL = 350 to 700 ml min-1). 6. From the results of the in vitro experiments it is concluded that cyclosporin A may potentially inhibit drug metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗