Calcium gluconate in severe verapamil intoxication.
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Aged↗
Biomedical subjects
M Wenk
Publications and source records attributed to M Wenk.
Determination of dextromethorphan and dextrorphan in urine by high-performance liquid chromatography after solid-phase extraction.
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Administration, Oral↗
Netilmicin in the neonate: population pharmacokinetic analysis and dosing recommendations.
Netilmicin pharmacokinetics were studied in neonates of 27 to 42 weeks' gestational age and 0.8 to 5.0 kg body weight in their first 2 weeks of life by the population pharmacokinetic approach. The data were best described by a two-compartment model. Clearance depends on body weight, gestational age, and postnatal age. Volume of distribution of the central and peripheral compartments was also related to body weight. Including these patient characteristics in the population pharmacokinetic regression model resulted in a marked reduction of the unexplained interindividual variability. This enabled us to derive dosage recommendations that result in peak and average concentrations within the desired range for 95% of the neonates with gestational age above 31 weeks, thus avoiding the need for individual drug-level monitoring in a well-defined large group of patients. Only for infants with gestational age less than 31 weeks who are less than 6 days old is individual dose adjustment based on serum concentration measurements required.
Body Weight↗
Population pharmacokinetics of tobramycin.
1. Population pharmacokinetic parameters of tobramycin were determined in a heterogenous group of 97 patients using serum samples drawn for the routine monitoring of tobramycin concentrations, following multiple dosing regimens. 2. To describe the accumulation kinetics of tobramycin a two-compartment pharmacokinetic model was required. The best fit to the data was obtained when drug clearance (1 h-1) was related linearly to creatinine clearance (proportionality constant: 0.059 +/- 0.002 x CLcr (ml min-1)) and initial volume of distribution (1) was related linearly to body weight (proportionality constant: 0.327 +/- 0.014 x body weight (kg)). The intersubject variability in these two parameters was 32% and 3%, respectively, whilst the residual or intrasubject variability amounted to 21% of the tobramycin concentration. The terminal half-life of tobramycin, 26.6 +/- 9.4 h, was appreciably shorter than previously reported. 3. The population pharmacokinetic model was validated against data obtained from 34 independent patients and the predicted and observed concentrations were found to be in good agreement. The population pharmacokinetic model was used to design a priori dosing recommendations for tobramycin.
Adolescent↗
Pharmacokinetics of cyclosporine G in patients with renal failure.
The pharmacokinetics of the cyclosporine A (CsA, Sandimmune) analogue Nva2-cyclosporine, or cyclosporine G (CsG) was investigated in 6 patients with terminal renal failure after a 4-hr intravenous infusion (3.5 mg/kg) and after oral administration (600 mg) of the drug. Blood samples were collected up to 38 hr and CsG concentrations were measured by radioimmunoassay and high-performance liquid chromatography. The resulting pharmacokinetic parameters of CsG were similar to those described for CsA in the same patient population. Based on HPLC determinations, a mean terminal elimination half-life of 18.9 hr was calculated. The total body clearance was 0.55 L/hr/kg, the volume of the central compartment was 0.32 L/kg, and the steady-state volume of distribution was 5.97 L/kg. After oral administration maximum CsG concentrations in blood were reached between 2.5 and 3 hr, and the bioavailability was in the range of 24-55% (mean 36%). The ratios between the polyvalent RIA and HPLC determinations were considerably larger after oral dosing than after i.v. infusion. The blood-to-plasma ratio was 1.23, which is smaller than that observed for CsA. These results suggest that in patients undergoing renal transplantation the same dosing strategies can be applied for CsG as have been established for CsA.
Adult↗
Measurements of cyclosporine A by RIA in different centers are not comparable.
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Cyclosporins↗
Use of ciprofloxacin in the treatment of Pseudomonas aeruginosa infections.
The therapeutic efficacy and safety of ciprofloxacin was studied in 30 patients with Pseudomonas aeruginosa infections. In 20 patients ciprofloxacin was given alone and in 10 patients (including 8 compromised hosts) in combination with an aminoglycoside (9) or azlocillin (1). Ciprofloxacin was given in doses of 500 mg orally or 200-300 mg i.v. every 12 h. In patients receiving only ciprofloxacin clinical cure with eradication of bacteria was obtained in 15 patients (75%) with infections of bone and joint (6), skin and soft tissue (4), lung (2), middle ear (2) and CSF (1). Two patients with lymphoma and Pseudomonas aeruginosa pneumonia died. In patients receiving combination therapy a definite therapeutic success was achieved in four (40%). Three patients with Pseudomonas aeruginosa septicemia died. In seven patients nine bacterial strains with decreasing susceptibility of ciprofloxacin (increase in MIC from less than or equal to 0.5 micrograms/ml to 2-16 micrograms/ml) were selected (6 Pseudomonas aeruginosa, 1 Enterobacter cloacae, 1 Serratia marcescens, 1 Staphylococcus aureus). Ciprofloxacin was well tolerated. This new quinolone seems to be suitable for single drug treatment of Pseudomonas aeruginosa infections in patients with normal host defense mechanisms, while its therapeutic potential in compromised hosts requires further evaluation.
Administration, Oral↗
Exercise-induced ventricular tachycardia as a manifestation of flecainide toxicity.
A 32-year-old woman with prolapsed mitral valve was treated with flecainide because of an episode of primary ventricular fibrillation. The drug was chosen because several hundred short runs of ventricular tachycardia unrelated to exercise were observed during 24-hour monitoring. Oral medication at a dose of 200 mg twice daily suppressed all repetitive ventricular ectopy. Eighteen months later, however, a further 24-hour recording showed a ventricular arrhythmia which was provoked early in the morning by exercise. Because the tablets were taken late in the evening and early in the morning it was suspected that toxic levels of flecainide may have produced the arrhythmia. Measurement confirmed this suspicion. Reducing the dosage abolished the arrhythmia.
Adult↗
Azlocillin serum levels on repetitive dosage in patients with normal and abnormal renal function.
Azlocillin serum concentrations were followed in 9 severely ill patients with various degrees of renal dysfunction after single and repetitive dosage. All patients were treated concomitantly with a cephalosporin and/or an aminoglycoside antibiotic. Elimination halflives (t1/2 beta) were highly variable (62-1, 194 min), but no significant increase occurred in patients with stable renal function during repetitive dosage due to previously described nonlinear pharmacokinetic behavior of azlocillin. However, drug accumulation was observed in patients with deterioration of renal and hepatic function. The rise in drug accumulation can be disproportionally high if both routes of elimination are affected. In such cases, careful dosage adjustment of azlocillin is required to avoid toxic side effects.
Adult↗
Serum half life of prostatic acid phosphatase.
Traumatic manipulation of the prostate can cause elevated prostatic acid phosphatase (PAP) values. To avoid falsely elevated PAP values after prostatic trauma we studied the serum half life of PAP and the time taken to return to preoperative levels in patients undergoing transurethral resection (TUR-P). Although we observed a broad variation in peak PAP values the half life of PAP is fairly constant at about 1.1-2.6 h. Preoperative values were reached within 30 h. We conclude that PAP determinations can safely be carried out 30 h after prostatic trauma without any risk of falsely elevated PAP values.
Acid Phosphatase↗
[Comparative studies on imaging artificial bone lesions--conventional tomography and computed tomography].
Conventional tomography (T) and computer tomography (CT) were used for examining 97 artificial bone lesions at various sites. The purpose of the study was to determine how far CT can replace T in the diagnosis of skeletal abnormalities. The results have shown that modern CT, particularly in its high resolution form, equals T and provides additional information (substrate of a lesion, its relationship to neighbouring tissues, simultaneous demonstration of soft tissues etc.). These cannot be shown successfully by T. It follows that CT is indicated as the primary method of examination for lesions of the facial skeleton, skull base, spine, pelvis and, to some extent, extremities.
Animals↗
Experience with NONMEM: analysis of serum concentration data in patients treated with mexiletine and lidocaine.
The generality and flexibility of the computer package NONMEM also confront the user with the difficult task of choosing the model which best describes the data at hand. With two practical examples we show how one may proceed in building the population model for serum concentration measurements. Features of NONMEM are presented which help the user to make the choice among different models.
Computers↗
Cyclosporine alone or in combination with prednisone in cadaveric renal transplantation.
One hundred recipients of first cadaveric kidney transplants were treated with three different immunosuppressive regimens: (1) conventional immunosuppression, (2) CsA alone, and (3) low-dose CsA in combination with low-dose prednisone, with rapid adjustment to give CsA whole blood trough levels of 300 to 800 ng/mL. One-year graft survival in the aza + pred group was 76%, and in the CsA alone group 75%. Graft survival at two and six months in the CsA-pred group was 94%. The dose of CsA in the CsA-pred group in the first two months posttransplant was only about half that given to the CsA-alone group. Surprisingly, the reduction in the CsA dose also reduced the number of methylprednisolone pulses given for treating rejection by greater than 50%. The incidence of nephrotoxicity and extrarenal side effects also fell considerably. Withdrawal of prednisone in the CsA-pred group after five months led to reversible rejection in two cases. In conclusion, (1) the rapid reduction in the CsA dosage is beneficial and has no drawbacks, and (2) our guidelines for withdrawing prednisone (timing of withdrawal, rate of reduction in dosage) still need further refinement.
Adult↗
Cyclosporin A used alone or in combination with low-dose steroids in cadaveric renal transplantation.
The actual survival rate of 25 primary cadaveric kidney grafts in recipients treated initially with cyclosporin A (CyA) alone was 84%. The survival rate in 37 patients under conventional immunosuppression was 76%. The mean number of dialyses required in the first 4 weeks after transplantation was 1.2 per patient in both groups. At 15-28 months posttransplant, mean serum creatinine levels have remained stable at 175 mumol/l in the CyA group. The mean daily dose of steroids (including methylprednisolone i.v.) in the first two months was 2.07 mg/kg/d in patients under conventional immunosuppression and 0.76 mg/kg/d in the patients receiving CyA (p less than 0.001). The combination of CyA with low-dose steroids enabled the dose of CyA to be rapidly tapered off in once-weekly steps. CyA levels were monitored by determination of whole blood trough concentrations (target level: 300-800 ng/ml). At 60 days posttransplant the average dose of CyA was 6.0 +/- 0.5 mg/kg/d compared with an average daily dose of 11.4 +/- 0.9 as recommended for CyA alone in the protocol for the European multicentre study. This more rapid reduction in the CyA dose reduced nephrotoxicity (serum creatinine levels 174 +/- 14 as compared with 289 +/- 31 mumol/l) (p less than 0.05) and almost halved the number of methylprednisolone pulses given up to the end of the second month. We conclude from these results (1) that previously the dosage of CyA administered at this centre was probably too high, and (2) early adjustment of dose levels on the basis of blood concentrations and with low-dose prednisone cover appears to be safe and effective, but requires further verification.
Azathioprine↗
Simultaneous determination of diprophylline, proxyphylline and theophylline in serum by reversed-phase high-performance liquid chromatography.
A selective and reliable high-performance liquid chromatographic assay for the simultaneous determination of diprophylline, proxyphylline and theophylline is described. The method involves a single extraction procedure followed by separation on an ODS reversed-phase column using a ternary solvent system. The assay is sufficiently rapid and sensitive to be applied for pharmacokinetic studies as well as for routine monitoring of patient's serum after therapeutic doses of the combined preparation. The practicability and utility of the proposed method is demonstrated in a pharmacokinetic study on four healthy volunteers.
Adult↗
Intravenous cyclosporine kinetics in renal failure.
Kinetics of the novel immunosuppressive cyclosporine were determined in four patients with terminal renal failure. After a short intravenous infusion (2.05 to 3.5 mg/kg in 4 hr), blood and plasma concentrations were measured (HPLC and radioimmunoassay [RIA] up to 36 hr. After infusion, concentration curves of the drug were characterized by a rapid initial fall (t 1/2 alpha 0.10 +/- 0.03 hr), followed by a biphasic elimination phase with corresponding t 1/2s of 1.08 +/- 0.25 hr (t 1/2 beta) and 15.8 +/- 8.4 hr (t 1/2 gamma). The volumes of distribution, calculated from whole blood concentrations (HPLC), were 0.140 +/- 0.48 l/kg (volume of the central compartment) and 3.49 +/- 2.65 l/kg (volume of distribution at steady state), whereas systemic clearances were 0.369 +/- 0.08 l/hr/kg. Blood levels measured by RIA exceeded the HPLC values after the fourth hour by up to 100%, indicating the production of cross-reacting cyclosporine metabolites. Plasma concentrations were considerably lower than in whole blood. Elimination of unchanged cyclosporine in patients with renal failure appears to be of the same order as in those with normal kidney function. Modification of the initial dosage regimens is therefore probably not required.
Chromatography, High Pressure Liquid↗
Reproducibility study of the pharmacokinetics of amikacin, gentamicin and tobramycin; a three-way crossover study.
The hypothesis that the pharmacokinetics of amikacin are more predictable than those of gentamicin or tobramycin was studied. In a three-way crossover design 58 volunteers received 7.5 mg/kg amikacin by iv infusion and either 1.5 mg/kg or 1 mg/kg gentamicin and tobramycin. The mean half-life and mean serum concentration at 1 h for each drug was determined. No consistent significant difference was found between the pharmacokinetics of amikacin and the other two drugs.
Amikacin↗
Cyclosporine in human bone marrow transplantation. Serum concentration, graft-versus-host disease, and nephrotoxicity.
Serum concentrations of cyclosporine were studied in 42 patients given cyclosporine for the prevention of graft-versus-host-disease (GVHD) following allogeneic bone marrow transplantation (BMT). Serum trough levels for cyclosporine were determined in each patient at least once weekly during the first 3 months and were compared with the occurrence of GVHD and with nephrotoxicity. Cyclosporine was given as 20 mg/kg i.m. or as a 24-hr infusion for the first 5-7 days. This was followed by a single daily oral dose of 12.5 mg/kg for 6 months. Cyclosporine was then gradually reduced and stopped after one year. After a median observation period of 2 years 25 of the 42 patients (59%) are alive. Twenty six patients (62%) developed GVHD, which was stage II or more in 11 (26%) and fatal in 2 patients (5%). Five patients developed GVHD 6-8 weeks after withdrawal of cyclosporine one year after BMT. All patients improved after restarting cyclosporine. No correlation between cyclosporine serum concentration and GVHD was observed, but patients with GVHD had greater fluctuations of their serum trough levels. Serum creatinine increased in all patients soon after BMT and was correlated with cyclosporine serum concentration during the first month. Serum creatinine, however, rose further despite lower cyclosporine concentrations in the second month. These results show that cyclosporine effectively reduces the severity, but not the incidence, of GVHD suggesting that there is a subset of cells resistant to cyclosporine. The therapeutic range, however, between high doses (which are often associated with nephrotoxicity) and the minimal effective dose of cyclosporine, has yet to be defined.
Adolescent↗