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Biomedical subjects

G R Matzke

Publications and source records attributed to G R Matzke.

At least 91 records · Page 5Linked to original sources
PubMed1987

Comparison of antihypertensive, renal hemodynamic, and humoral effects of pinacidil and hydralazine monotherapy.

The antihypertensive, renal hemodynamic, and humoral effects of pinacidil and hydralazine monotherapy were compared in a double-blind study. Supine diastolic blood pressure decreased with pinacidil (n = 14) from 96.5 to 82.6 mmHg (p less than 0.05), after a mean of 8.5 weeks at a mean dose of 64.3 mg/day, and with hydralazine (n = 15) from 101.5 to 94.0 mmHg (p less than 0.05), after 8.3 weeks at a dose of 163.3 mg/day. Renal plasma flow, glomerular filtration rate, and urinary albumin excretion did not change with pinacidil or hydralazine therapy. Neither agent altered plasma renin activity. Supine and upright plasma aldosterone concentrations decreased significantly during pinacidil, but not during hydralazine, therapy. Thus, both pinacidil and hydralazine reduced blood pressure and preserved renal function. During pinacidil therapy, plasma aldosterone concentrations decreased, whereas plasma renin activity did not. The mechanism of this response is unclear.

Adolescent↗
PubMed1987

Aminoglycoside redistribution phenomenon after hemodialysis: netilmicin and tobramycin.

The serum concentration time profile of netilmicin and tobramycin before, during, and after hemodialysis was assessed in 5 noninfected adult chronic hemodialysis patients. The pharmacokinetic profile was biexponential for both agents in the pre-hemodialysis period. The total body clearance of netilmicin was significantly greater than that of tobramycin (5.32 +/- 0.75 ml/min vs 3.66 +/- 1.00 ml/min; p less than 0.05). The hemodialysis clearances of netilmicin and tobramycin were similar (60.8 +/- 16.6 ml/min and 54.7 +/- 18.8 ml/min, respectively). Netilmicin and tobramycin serum concentrations increased significantly 10 minutes after cessation of hemodialysis and maximally rebounded to 38.3 +/- 16.2% and 18.3 +/- 3.0% at 1.7 +/- 0.3 hours and 1.9 +/- 0.7 hours, respectively. This phenomenon may be a primary contributor to the marked variability observed in the clinical pharmacokinetics of these agents in hemodialysis patients. These data suggest that clinical serum concentrations should not be drawn until two hours after hemodialysis.

Adult↗
PubMed1987

Effects of cyclosporine on the isolated perfused rat kidney.

Although cyclosporine (CsA) has been shown to cause decreased renal function in humans, the mechanisms important in cyclosporine nephrotoxicity are not well understood. Investigations of cyclosporine nephrotoxicity in animal models have been complicated by systemic toxic effects not seen in humans. In the present study, the direct renal effects of cyclosporine were investigated in the isolated perfused rat kidney (IPRK) model. Cyclosporine delivered by nontoxic liposomes had no effect on IPRK resistance, perfusate flow, inulin clearance, or fractional reabsorption of sodium, despite marked tissue accumulation of CsA (55.1 +/- 7.2 micrograms/g kidney tissue). In contrast, a 63% decrease in inulin clearance was observed following the administration of intravenous cyclosporine (0.1 ml). However, similar changes in IPRK function were seen after the administration of 0.1 ml of the intravenous cyclosporine vehicle, cremophor, suggesting that the alterations in function were secondary to the vehicle. All together, these findings suggest that cyclosporine nephrotoxicity may be secondary to renal innervation, toxic metabolites, or other systemic effects of cyclosporine not present in the IPRK.

Animals↗
PubMed1987

Improved liquid-chromatographic assay of labetalol in plasma.

This is an assay for labetalol in plasma by "high-performance" liquid chromatography, with 5-(2-[4-(4-chlorophenyl)ethyl]) salicylamide hemihydrate as the internal standard. Plasma samples (500 microL) are extracted with acetonitrile, evaporated under nitrogen, reconstituted in the mobile phase, and injected onto a PRP-1 (Hamilton) column packed with particles of poly(styrene-divinylbenzene) copolymer. Fluorescence, enhanced by post-column introduction of NH4OH, was measured in the effluent (excitation wavelength 340 nm, emission wavelength 418 nm). Retention times for labetalol and the internal standard were 1.99 and 3.32 min, respectively. Inter- and intraday CVs for high and low concentrations of the drug were less than 7.5%. The assay standard curve is linear from 1 to 250 micrograms/L. Some commonly co-administered drugs were tested and did not interfere.

Chromatography, High Pressure Liquid↗
PubMed1986

Disposition of vancomycin during hemofiltration.

The disposition of vancomycin was assessed in five patients receiving hemofiltration after intravenous dosing with an 18 mg/kg dose after a hemofiltration procedure. The serum concentration-time profile was characterized before, during, and after the next hemofiltration procedure. The t 1/2 of vancomycin was 136.0 +/- 27.2 hours (mean +/- SD) before hemofiltration and 4.1 +/- 1.2 during hemofiltration. Approximately 400 mg of vancomycin was recovered in the filtrate and the hemofiltration clearance was 152.6 +/- 21.5 ml/min. A significant relationship was observed between vancomycin clearance and ultrafiltration flow rate (r = 0.9914). A marked rebound in vancomycin serum concentration (52.4% +/- 15.6%) was observed in all patients. Hemofiltration has a significant effect on the disposition of vancomycin. Because of the marked interpatient variability in elimination t 1/2 and the degree and time course of the rebound, an individualized approach to vancomycin therapy in this patient population is recommended.

Aged↗
PubMed1986

The disposition and dynamics of labetalol in patients on dialysis.

The disposition of labetalol was assessed in 16 patients on dialysis after intravenous dosing with 0.7 to 1.0 mg/kg during an interdialytic period and just before hemodialysis (n = 8) and during continuous ambulatory peritoneal dialysis (CAPD) (n = 8). The plasma concentration time data exhibited triexponential decay in all patients. The terminal t 1/2 of labetalol was 12.90 +/- 4.68 hours, the total body clearance was 1198.2 +/- 249.4 ml/min, and the AUC was 921.4 +/- 175.2 ng hr/ml during the interdialytic period. No significant changes were observed in these parameters after dosing with labetalol just before dialysis. The hemodialysis clearance of labetalol was 30.67 +/- 5.49 ml/min, and only 0.189 +/- 0.042 mg of labetalol was removed by hemodialysis. The terminal t 1/2 averaged 13.05 +/- 6.32 hours during CAPD. Steady-state volume of distribution, total body clearance (Clp), and CAPD clearance were 10.39 +/- 2.77 L/kg, 1397.2 +/- 372.3 ml/min, and 1.94 +/- 0.65 ml/min, respectively. The fraction of the dose recovered in the CAPD dialysate during the 72-hour study period was 0.14% +/- 0.09%. The decay of the antihypertensive effect of labetalol was gradual and paralleled the decline in the log plasma concentration. There was a significant correlation between labetalol plasma concentration and the fall in supine diastolic and mean blood pressure after the interdialytic dose and during CAPD. Although labetalol is removed by dialysis, dialysis does not significantly enhance Clp.

Adult↗
PubMed1986

Disposition of cefotaxime and desacetyl cefotaxime during continuous ambulatory peritoneal dialysis.

The disposition of cefotaxime (CTX) and desacetyl cefotaxime (DAC) was studied in eight noninfected patients on continuous ambulatory peritoneal dialysis. Each patient received a single intravenous (i.v.) infusion and an intraperitoneal (i.p.) instillation of 2 g of CTX. Multiple blood and dialysate samples were collected during the 72-h period after drug administration. The half-life, steady-state volume of distribution, and total body clearance of CTX following i.v. administration were 2.2 +/- 1.0 h (mean +/- standard deviation), 0.17 +/- 0.03 liters/kg, and 81.0 +/- 31.0 ml/min, respectively. No significant differences were observed in these parameters after i.p. administration. The continuous ambulatory peritoneal dialysis clearances of CTX and DAC were 1.82 +/- 0.43 and 2.84 +/- 0.70 ml/min, respectively, after i.v. administration. The bioavailability of CTX after i.p. instillation was 74.6 +/- 21.3%. Peak peritoneal dialysate CTX and DAC concentrations of 264.3 and 25.8 mg/liter, respectively, were observed after i.p. dosing. Administration (i.v.) of 2 g every 12 h or i.p. instillation of 2 g every 24 h may be used for the treatment of i.p. infections with highly susceptible organisms (MIC less than 1.0 microgram/ml).

Aged↗
PubMed1986

Lack of pharmacodynamic interaction between pentoxifylline and warfarin in the rat.

Pentoxifylline is a new hemorrheologic agent which decreases platelet aggregation and reduces fibrinogen levels. Its ability to affect the coagulation cascade was studied in rats with and without the coadministration of warfarin. There was no significant difference between the prothrombin time ratio (PTR) of the warfarin group (1.51 +/- 0.38) and the combination drug group (1.47 +/- 0.30) at 6 hours. Likewise, there was no significant difference between the PTR of the control group (1.09 +/- 0.07) and the group administered pentoxifylline alone (1.05 +/- 0.06). Although the mechanisms of action of the two drugs may overlap, the pharmacodynamic activity of warfarin was not significantly altered when pentoxifylline was coadministered.

Animals↗
PubMed1986

The effect of hemodialysis on piperacillin pharmacokinetics.

The disposition of piperacillin given as a 4 gm i.v. infusion was assessed during an interdialytic period and during hemodialysis in 12 chronic hemodialysis patients. Piperacillin concentrations in serum and dialysate were determined by HPLC. The half-life decreased from 2.84 +/- 2.04 h (mean +/- SD) during the interdialytic period to 1.30 +/- 0.43 h during the hemodialysis period (p = 0.008). Piperacillin total body clearance was 74.9 +/- 34.0 ml/min during the interdialytic period and the hemodialysis clearance was 92.4 +/- 30.0 ml/min. A significant change in the volume of distribution was observed from the interdialytic to dialytic period (0.21 +/- 0.06 vs 0.26 +/- 0.07 l/kg) (p = 0.026). A significant correlation between the hemodialysis clearance of piperacillin and hemodialysis clearance of creatinine and blood flow rate was also noted. No significant rebound in serum piperacillin concentrations was observed after cessation of hemodialysis. Approximately 46% of the amount of piperacillin in the body was removed by dialysis.

Adult↗
PubMed1986

Erythropoietin kinetics in rats: generation and clearance.

Detailed studies to analyze the early events of erythropoietin (Ep) secretion and clearance were performed in a rat model using a double antibody radioimmunoassay. Ep clearance was determined following intravenous injection of 1 mL of Ep-rich plasma, 1,080 mU/mL, obtained from phlebotomized rats. Analysis revealed a disappearance curve that conformed to a two-compartment model with an alpha half-life t1/2 of 3.6 minutes and a beta t1/2 of 86 minutes. The volume of distribution was similar to the calculated plasma volume. In anephric animals, there was no change in the plasma clearance rate or the volume of distribution. Rapid Ep secretion was elicited by a single 15 mL/kg phlebotomy (hematocrit decrement 45% to 30%), so that levels reached 20 to 30 times baseline (524 +/- 76 v 24 +/- 7 mU/mL) at five hours, whereas they plateaued for at least 33 hours. The increase in the rate of secretion was geometric, from 9.9 mU/h baseline secretion to 429 mU/h. These data identify a very sensitive and rapidly responsive system for Ep modulation in the rat.

Animals↗
PubMed1985

Cefotaxime and desacetyl cefotaxime kinetics in renal impairment.

Cefotaxime and desacetyl cefotaxime kinetics after a single, 1 gm intravenous dose were evaluated in five groups of subjects: group I, normal creatinine clearance (CLCR greater than 90 ml/min); group II, mild renal insufficiency (CLCR 30 to 89 ml/min); group III, moderate renal insufficiency (CLCR 16 to 29 ml/min); group IV, severe renal insufficiency (CLCR 4 to 15 ml/min); and group V, end-stage renal disease requiring maintenance hemodialysis (CLCR less than 6 ml/min). The steady-state volume of distribution (Vss) ranged from 10% to 55% of body weight but was not related to CLCR. The terminal t1/2 values of cefotaxime and desacetyl cefotaxime were 0.79 and 0.70, 1.09 and 3.95, 1.55 and 5.65, 2.54 and 14.23, and 1.63 and 23.15 hours in groups I to V, respectively. There were no significant changes in Vss or t1/2 after multiple dosing, but there were significant correlations between CLCR and cefotaxime total body clearance, cefotaxime and desacetyl cefotaxime renal clearance, and cefotaxime nonrenal clearance. Dosage regimens for the use of cefotaxime in patients with renal impairment are proposed.

Acute Kidney Injury↗
PubMed1985

Protein binding of disopyramide and elevated alpha-1-acid glycoprotein concentrations in serum obtained from dialysis patients and renal transplant recipients.

A rapid ultrafiltration technique was used to measure the free (unbound) fraction of disopyramide in serum obtained from 14 normal volunteers, 6 chronic hemodialysis patients, and 10 renal transplant recipients. The disopyramide-free fraction varied more than tenfold at a corresponding total (free plus bound) serum disopyramide concentration of 3 micrograms/ml and was related to the concentration of an acute-phase protein, alpha-1-acid glycoprotein (AAG), in patient serum. Moreover, disopyramide-free fraction values were nearly twofold lower than normal in serum specimens obtained from those renal patients and transplant recipients with corresponding AAG serum concentrations greater than 100 mg/100 ml. AAG concentrations varied tenfold in patient serum and were on average nearly three times higher than AAG concentrations in normal volunteer serum. These findings suggested that the free fraction of disopyramide and possibly other drugs which bind extensively to AAG may be lower, and the interpatient variability in drug binding may be much more pronounced in serum obtained from hemodialysis patients and transplant recipients than previously recognized.

Adult↗
PubMed1984

Contribution of 5-(4-hydroxyphenyl)-5-phenylhydantoin to the discrepancy between phenytoin analyses by EMIT and high-pressure liquid chromatography.

Recently, phenytoin concentrations determined by enzyme multiplied immunoassay technique (EMIT) have been reported to be significantly elevated when compared to other assay methods in patients with end-stage renal disease (ESRD). We compared the plasma and plasma ultrafiltrate concentrations of phenytoin determined by EMIT and high-pressure liquid chromatography (HPLC) in a group of patients with normal renal function (NRF) and ESRD. The relationship between the degree of discrepancy in phenytoin concentrations in plasma and plasma ultrafiltrate and the concentration of combined (unconjugated plus conjugated) 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPHcom) was also assessed. The concentration of phenytoin in plasma and plasma ultrafiltrate measured by EMIT in the ESRD patients and the plasma ultrafiltrate concentrations of phenytoin in the NRF patients was significantly higher than the HPLC values. The mean concentrations of unconjugated HPPH (HPPHunconj) in plasma and plasma ultrafiltrate were not significantly different between the two patient groups. However, the concentration of HPPHcom in plasma and plasma ultrafiltrate specimens were significantly elevated in the ESRD patients. Orthogonal regression analysis of the relative error between the EMIT and HPLC phenytoin determinations and HPPHcom concentrations suggest that HPPHcom significantly correlates with the false elevation of phenytoin measurements in plasma and plasma ultrafiltrate. In patients with ESRD, phenytoin concentrations should be determined by either gas chromatography, HPLC, or fluorescence polarization.

Chromatography, High Pressure Liquid↗
PubMed1984

Hemodialysis elimination rates and clearance of gentamicin and tobramycin.

The apparent hemodialyzer elimination rate constant and clearance for gentamicin and tobramycin were determined during 100 routine hemodialysis treatments in 49 patients. Three different dialyzers (CDAK 3500, CF 1211, and CF 1511), which vary in membrane composition, surface area, and thickness, were evaluated. The elimination rate constant in each patient was calculated from the slope of the log serum concentration-time curves. Two different elimination rate constants for each patient were derived, one during hemodialysis (KT) and one off hemodialysis (K). The hemodialyzer elimination rate constant (KD) for each dialyzer was calculated as the difference between these two values. The hemodialyzer clearance (Cd) was calculated by multiplying the hemodialyzer elimination rate constant by the volume of distribution of the patient. The KDS of gentamicin and tobramycin by the three dialyzers were significantly different. The gentamicin KD of the CDAK 3500 was lower than the values of the CF 1211 and CF 1511 (0.086 versus 0.123 versus 0.131 h-1, respectively). The Cd of the CDAK 3500 for gentamicin was also significantly lower than that of the CF 1511. Although the CdS of tobramycin for the CF 1211 and CF 1511 were 24 and 43% greater than that for the CDAK 3500, these differences were not statistically significant. The KD and Cd of tobramycin were greater than those of gentamicin for all three dialyzers. These data demonstrate that commonly used hemodialyzers vary markedly with respect to their elimination and clearance characteristics of gentamicin and tobramycin. Clinically, these observations may be helpful in designing the correct dose of gentamicin and tobramycin to achieve maximum drug safety and efficacy in hemodialysis patients.

Aged↗