Simultaneous determination of mycophenolate and its metabolite mycophenolate-7-o-glucuronide with an isocratic HPLC-UV-based method in human plasma and stability evaluation.

Objectives: Mycophenolic acid (MPA) is an immunosuppressive agent which is commonly used in a fixed dose regime in solid organ transplantation. For clinical trials and therapeutic drug monitoring measuring plasma concentrations is necessary. Also, stability issues have to be addressed.

Ch14.18 antibody produced in CHO cells in relapsed or refractory Stage 4 neuroblastoma patients: a SIOPEN Phase 1 study.

Purpose: This study aimed to assess the safety, pharmacokinetic and activity profiles of the human-mouse chimeric monoclonal anti-disialoganglioside GD2 antibody ch14.18 produced in Chinese hamster ovary (CHO) cells (ch14.18/CHO).

Differential impact of the CYP3A5*1 and CYP3A5*3 alleles on pre-dose concentrations of two tacrolimus formulations.

Objectives: We investigated the pharmacokinetic and pharmacogenetic implications of conversion from a twice-daily (P-Tac) to a once-daily (A-Tac) tacrolimus (Tac) formulation.

Methods: We analyzed Tac levels in a cohort of 41 renal transplant patients with a stable graft function over a period of 1 year before and after conversion.

Results: After conversion, the patients had, on average, significantly lower Tac trough and dose-normalized trough levels (14%, P=0.

Carbamazepine and lamotrigine plasma concentrations in epileptic patients during optimising therapy.

Therapeutic monitoring of antiepileptic drugs is important in process of optimisation of therapy of epileptic patients. Carbamazepine (CBZ) and Lamotrigine (LMT) are important drugs in therapy of epileptic patients which requires the monitoring of concentration of these drugs in serum. Ourstudy aim was the comparison and interpretation of the results of routine therapeutic monitoring of Carbamazepine and Lamotrigine in spotlight of antiepileptic therapy optimisation.

Moxifloxacin does not alter ciclosporin pharmacokinetics in transplant patients: a multiple-dose, uncontrolled, single-centre study.

Background: Moxifloxacin has a broad antibacterial spectrum and rapid bactericidal activity, and is thus a good option for the treatment of bacterial infections in patients who have undergone organ or bone marrow transplantation. Transplant patients also receive immunosuppressant therapy such as ciclosporin.

Objective: The primary objective of this study was to assess the steady-state pharmacokinetics of ciclosporin with and without concomitant treatment with moxifloxacin in transplant recipients.

Prospectively assessed changes in lamotrigine-concentration in women with epilepsy during pregnancy, lactation and the neonatal period.

Purpose: To prospectively analyse the pharmacokinetics of lamotrigine (LTG) during pregnancy and lactation in a consecutive series of epileptic pregnant women.

Methods: Nine women on LTG-monotherapy were studied during pregnancy, delivery and lactation, until a mean of 3 weeks postpartum. Maternal blood samples were available from all trimesters as well as umbilical cord blood samples of the newborn 24 and/or 48 h postpartum.

St John's wort extract (Ze 117) does not alter the pharmacokinetics of a low-dose oral contraceptive.

Purpose: St John's wort (Hypericum perforatum) is an herbal remedy that is widely used in the treatment of depression. Recent clinical data have demonstrated that St John's wort extracts interfere with the action of various drugs and possibly also with combined oral contraceptives. Therefore, we investigated the effects of a St John's wort extract (Ze 117) with low hyperforin content on the pharmacokinetics of ethinylestradiol and 3-ketodesogestrel.

Endothelin-1 gene variant Lys198Asn and plasma endothelin level in obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a recognized risk factor for cardiovascular disorders. Thus, an association between endothelin-1 (EDN1) and OSA can be assumed. We investigated a cohort of 364 consecutive patients (age 57 +/- 10 years) with mild to severe OSA for the EDN1 variant Lys198Asn (G/T) and endothelin plasma levels and compared them with 57 controls.

Enantiospecific pharmacokinetics of metoprolol in CYP2D6 ultra-rapid metabolizers and correlation with exercise-induced heart rate.

Objective: Our objective was to study the enantioselective pharmacokinetics of metoprolol in CYP2D6 ultra-rapid metabolizers (UM) compared with extensive (EM) and poor (PM) metabolizers to quantify differential effects of metoprolol enantiomers on the beta1-adrenoreceptor blockade.

Methods: Twenty-nine healthy individuals were selected based on their CYP2D6 genotype, and 100 mg racemic metoprolol was administered. Plasma concentrations of R- and S-metoprolol and the metabolites SS-, SR-, RS-, and RR-hydroxymetoprolol were quantified by high-performance liquid chromatography.

Forces in anterior cruciate ligament during simulated weight-bearing flexion with anterior and internal rotational tibial load.

This study determined in-vitro anterior cruciate ligament (ACL) force patterns and investigated the effect of external tibial loads on the ACL force patterns during simulated weight-bearing knee flexions. Nine human cadaveric knee specimens were mounted on a dynamic knee simulator, and weight-bearing knee flexions with a 100N of ground reaction force were simulated; while a robotic/universal force sensor (UFS) system was used to provide external tibial loads during the movement. Three external tibial loading conditions were simulated, including no external tibial load (termed BW only), a 50N anterior tibial force (ATF), and a 5Nm internal rotation tibial torque (ITT).

Effects of the CYP2D6 gene duplication on the pharmacokinetics and pharmacodynamics of tramadol.

The analgesic drug tramadol is bioactivated by CYP2D6 to the opioid receptor agonist O-desmethyltramadol. Case reports indicated that carriers of the CYP2D6 gene duplication may be at high risk for opioid adverse events. However, the effects of the CYP2D6 duplication on kinetics and dynamics of tramadol have not been systematically studied.

Accelerating large cardiac bidomain simulations by arnoldi preconditioning.

Bidomain simulations of cardiac systems often in volve solving large, sparse, linear systems of the form Ax=b. These simulations are computationally very expensive in terms of run time and memory requirements. Therefore, efficient solvers are essential to keep simulations tractable.

Pharmacokinetics and pharmacodynamics of mycophenolic acid after enteric-coated mycophenolate versus mycophenolate mofetil in patients with progressive IgA nephritis.

Mycophenolic acid can be administered orally using mycophenolate mofetil or enteric-coated mycophenolate. In renal transplant patients on immunosuppressant combination therapy, the overall mycophenolic acid exposure after oral dosing with mycophenolate mofetil and enteric-coated mycophenolate is similar. This study compared pharmacokinetics and pharmacodynamics of mycophenolic acid after equivalent doses of enteric-coated mycophenolate (360 mg twice daily) or mycophenolate mofetil (500 mg twice daily) in 7 patients with progressive IgA nephritis (glomerular filtration rate 20-35 mL/min) using a randomized crossover design.

Reduced-order preconditioning for bidomain simulations.

Simulations of the bidomain equations involve solving large, sparse, linear systems of the form Ax = b. Being an initial value problems, it is solved at every time step. Therefore, efficient solvers are essential to keep simulations tractable.

Conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in maintenance renal transplant recipients receiving tacrolimus: clinical, pharmacokinetic, and pharmacodynamic outcomes.

Background: Mycophenolic acid (MPA) pharmacokinetics using the mycophenolate mofetil (MMF) formulation are known to differ between patients receiving tacrolimus or cyclosporine, but only limited data exist concerning concomitant use of tacrolimus and enteric-coated mycophenolate sodium (EC-MPS).

Methods: In this six-month, multicenter, open-label, single-arm trial, 63 maintenance renal transplant patients receiving tacrolimus were converted from mycophenolate mofetil (MMF) to EC-MPS.

Results: MPA concentration-time profiles in 21 patients showed that MPA exposure was similar with MMF or EC-MPS (mean area under the curve 39.

Pharmacokinetics and pharmacodynamics of rosiglitazone in relation to CYP2C8 genotype.

Objectives: Rosiglitazone is metabolically inactivated predominantly via the cytochrome P450 (CYP) enzyme CYP2C8. The functional impact of the CYP2C8*3 allele coding for the Arg139Lys and Lys399Arg amino acid substitutions is controversial. The purpose of this was to clarify the role of this polymorphism with regard to the pharmacokinetics and clinical effects of rosiglitazone.

Effects of fluvastatin and cigarette smoking on CYP2C9 activity measured using the probe S-warfarin.

Objective: The effect of cigarette smoking on CYP2C9 activity is unknown. We conducted a study to evaluate whether there is a difference in CYP2C9 activity in smokers versus non-smokers by examining S-warfarin AUC after CYP2C9 inhibition with fluvastatin. In addition, the effect of the CYP2C9 inhibitor fluvastatin was evaluated using S-warfarin as a probe.

The extent of induction of CYP3A by St. John's wort varies among products and is linked to hyperforin dose.

Objective: Induction of CYP3A by St. John's wort (SJW) extracts with high hyperforin (HYF) content is well described. Since SJW products vary in the amount of HYF and other main constituents, the aim of the study was to evaluate the effect on CYP3A function of SJW preparations with a range from very low to high HYF content.

Approaching an individual methotrexate regimen in leptomeningeal carcinomatosis.

Background: Chemotherapeutic effects in leptomeningeal carcinomatosis (LC) vary widely between patients, presumably in part because drug elimination from cerebrospinal fluid (CSF) differs between individuals. An individual dosing, adapted to elimination, may improve treatment efficacy.

Objective: To discuss the feasibility of easily accessible elimination parameters for an individual dosing of chemotherapy in LC.

No relevant interaction with alprazolam, caffeine, tolbutamide, and digoxin by treatment with a low-hyperforin St John's wort extract.

We evaluated the pharmacokinetic interaction between a low-hyperforin St John's wort (SJW) extract and alprazolam, caffeine, tolbutamide, and digoxin. Previous reports on other SJW products had shown remarkably decreased plasma concentrations of certain co-medicated drugs, which was attributed to an inducing effect of SJW on cytochrome P-450 (CYP) and p-glycoprotein (p-gp) activity. Two randomised, placebo-controlled studies were performed with 28 healthy volunteers (age 18 - 55 years) in each study.

Quantification of pravastatin in human plasma and urine after solid phase extraction using high performance liquid chromatography with ultraviolet detection.

A high performance liquid chromatography (HPLC) method for the estimation of pravastatin in human plasma and urine samples has been developed. The preparation of the samples was performed by automated solid phase extraction using clonazepam as internal standard. The compounds were separated by isocratic reversed-phase HPLC (C(18)) and detected at 239 nm.

Parallel multigrid preconditioner for the cardiac bidomain model.

The bidomain equations are widely used for the simulation of electrical activity in cardiac tissue but are computationally expensive, limiting the size of the problem which can be modeled. The purpose of this study is to determine more efficient ways to solve the elliptic portion of the bidomain equations, the most computationally expensive part of the computation. Specifically, we assessed the performance of a parallel multigrid (MG) preconditioner for a conjugate gradient solver.

MCG to ECG source differences: measurements and a two-dimensional computer model study.

In this work we combine body surface potential map (BSPM) and magnetocardiogram (MCG) measurements with computer simulations in order to elucidate a recent thesis that claims the orthogonality of the main sources of MCG and ECG. Body surface currents and MCG pseudo currents are calculated from measured BSPM and MCG data, respectively. In contrast to the MCG-ECG source orthogonality thesis, we observe the main orientation of the BSPM currents and MCG pseudo currents to have similar axis during most of the depolarization R wave.

MDR1 haplotypes derived from exons 21 and 26 do not affect the steady-state pharmacokinetics of tacrolimus in renal transplant patients.

Aim: This retrospective study investigated the influence of MDR1 haplotypes derived from the polymorphisms 2677G > T (exon 21) and 3435C > T (exon 26) on the pharmacokinetics of the immunosuppressant drug tacrolimus in 73 renal transplant patients.

Methods: Based on both variants of SNPs 2677 and 3435, four different haplotypes and eight different genotypes were identified in the study sample. Tacrolimus trough concentrations (C(0)) were compared between different SNP variants and genotypes, as well as between carriers and noncarriers of each haplotype.