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Biomedical subjects

K M Sowinski

Publications and source records attributed to K M Sowinski.

At least 19 recordsLinked to original sources
PubMed2004

Determination of ciprofloxacin concentrations in human serum and urine by HPLC with ultraviolet and fluorescence detection.

OBJECTIVE: To develop a simple and sensitive high performance liquid chromatography method for the determination of ciprofloxacin concentrations in human serum and urine. METHOD: Serum proteins were removed by ultrafiltration through a filtering device after the addition of a displacing reagent. Urine samples were diluted with mobile phase prior to injection. Separation was achieved with a C18 reverse-phase column and using ultraviolet (UVD) and fluorescence detection (FD) for serum samples and UVD for urine samples. RESULTS: The quantitation limits of the assay were 20 ng/ml (FD) and 100 ng/ml (UVD) in serum and 1 microg/ml in urine. The assay was successfully applied to a pharmacokinetic study of ciprofloxacin in healthy volunteers. CONCLUSION: The method presented for ciprofloxacin assay in human serum and urine requires less sample clean up and is more sensitive than those reported in the literature.

Anti-Infective Agents↗
PubMed2001

Regulation of human beta(1)-adrenergic receptors and their mRNA in neuroepithelioma SK-N-MC cells: effects of agonist, forskolin, and protein kinase A.

We determined the effect of long-term exposure to beta-agonists on beta(1)-adrenergic receptors (beta(1)-AR) in human neuroepithelioma SK-N-MC cells because earlier studies have indicated that beta(1)-AR in this cell line are resistant to agonist-induced down-regulation. Exposing SK-N-MC cells to isoproterenol for 24 hr reduced the density of beta(1)-AR by 72%, whereas forskolin, an activator of all the isoforms of adenylyl cyclase, failed to affect the density of beta(1)-AR. Measurement of beta(1)-AR mRNA levels by the ribonuclease protection assay revealed that isoproterenol-induced down-regulation of beta(1)-AR was associated with a sharp decline in beta(1)-AR mRNA, while forskolin also failed to affect this parameter. The differences between the effects of isoproterenol and forskolin on beta(1)-AR were unrelated to cyclic AMP levels, since both agents increased cyclic AMP equally. Next, we determined the role of cyclic AMP-dependent protein kinase A (PKA) in this phenomenon. Inhibition of PKA by its specific inhibitor, H-89 [N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide, 2HCl], markedly reduced the magnitude of the isoproterenol-mediated down-regulation of the beta(1)-AR and its mRNA. Transient expression of the catalytic subunit of PKA in SK-N-MC cells down-regulated beta(1)-AR independently of isoproterenol. Therefore, PKA is central to the effect of beta-agonists in down-regulating beta(1)-AR, and its spatial compartmentalization and access to the receptor appear to be essential components of its action.

Adrenergic Agonists↗
PubMed2001

Determination of albumin and myoglobin in dialysate and ultrafiltrate samples by high-performance size-exclusion chromatography.

A high-performance size-exclusion chromatographic method was developed, validated and implemented for simultaneous and quantitative determination of albumin and myoglobin along with inulin, vancomycin and creatinine in dialysate and ultrafiltrate samples from in vitro hemodialysis experiments. The experimental parameters including mobile phase pH, ionic strength, detection wavelength, flow-rate, injection volume were first optimized for the determination of albumin, myoglobin, inulin, vancomycin and creatinine. The peak height ratio and detection limits of the proteins were then comparatively studied at 210, 254 and 280 nm by UV and diode array detection. The method was further validated by evaluating the linearity, precision and accuracy of the proteins. The assay was finally implemented to the simultaneous and quantitative determination of the proteins in dialysate and ultrafiltrate samples.

Albumins↗
PubMed2001

Meropenem pharmacokinetics in children and adolescents receiving hemodialysis.

The emergence of multi-drug-resistant bacteria is of great concern to the care of pediatric end-stage renal disease (ESRD) patients who receive either hemodialysis or peritoneal dialysis via a catheter. Infections with gram-negative organisms, especially Pseudomonas aeruginosa, are difficult to eradicate and often necessitate catheter removal. Meropenem, a broad-spectrum antibiotic of the carbapenem class of beta-lactams, is effective against most gram-positive and gram-negative bacteria and has enhanced activity against P. aeruginosa. We studied the pharmacokinetics of meropenem during and between hemodialysis treatments in seven pediatric patients. Meropenem was given as a single dose of 20 mg/kg (maximum 500 mg) before and after two separate hemodialysis treatments. Meropenem administration was tolerated without any adverse effects. Hemodialysis effectively cleared meropenem in a manner that correlated with percent urea reduction. Median drug half-life was 7.3 h off dialysis (range 4.9-11.7 h). The dose of 20 mg/kg was not sufficient to produce an acceptable interdialytic pharmacodynamic profile of 70% duration with a meropenem concentration >4 microg/ml, the MIC90 of meropenem for P. aeruginosa. Dosing simulations revealed that a daily dose of 25 mg/kg or an alternate day dose of 40 mg/kg would result in an acceptable pharmacodynamic profile. Both simulated doses achieved acceptable peak concentrations.

Adolescent↗
PubMed2001

Cefazolin dialytic clearance by high-efficiency and high-flux hemodialyzers.

Cefazolin dialytic clearance has not been determined in patients undergoing hemodialysis with high-efficiency or high-flux dialyzers. The objective of this study is to determine the pharmacokinetics and dialytic clearance of cefazolin and develop dosing strategies in these patients. Twenty-five uninfected subjects undergoing chronic thrice-weekly hemodialysis were administered a single dose of intravenous cefazolin (15 mg/kg) after their standard hemodialysis session. Fifteen subjects underwent hemodialysis with high-efficiency hemodialyzers, and 10 subjects underwent hemodialysis with high-flux hemodialyzers. Blood and urine samples were collected serially over the interdialytic period, during the next intradialytic period, and immediately after the next hemodialysis session. Serum and urine concentrations of cefazolin were determined by high-performance liquid chromatography. Differential equations describing a two-compartment model were fit to the cefazolin serum concentration-time data over the study period, and pharmacokinetic parameters were determined. Mean dialytic clearance values for cefazolin were significantly greater in the high-flux group compared with the high-efficiency group (30.9 +/- 6.52 versus 18.0 +/- 6.26 mL/min, respectively; P: < 0.05). Cefazolin reduction ratios were significantly greater (0.62 +/- 0.08 versus 0.50 +/- 0.07; P: < 0.005) in the high-flux group compared with the high-efficiency group and correlated well with equilibrated urea reduction. The pharmacokinetic model developed from patient data was used to simulate cefazolin serum concentration data for high-efficiency and high-flux dialyzers. Cefazolin doses of 15 or 20 mg/kg after each hemodialysis session maintained adequate serum concentrations throughout a 2- or 3-day interdialytic period regardless of hemodialyzer type.

Adult↗
PubMed2000

Noni juice (Morinda citrifolia): hidden potential for hyperkalemia?

We report the case of a man with chronic renal insufficiency who self-medicated with an alternative medicine product known as noni juice (Morinda citrifolia). The patient presented to the clinic with hyperkalemia despite claiming adherence to a low-potassium diet. The potassium concentration in noni juice samples was determined and found to be 56.3 mEq/L, similar to that in orange juice and tomato juice. Herbal remedies and alternative medicine products may be surreptitious sources of potassium in patients with renal disease.

Beverages↗
PubMed2000

Vancomycin assay performance in patients with end-stage renal disease receiving hemodialysis.

STUDY OBJECTIVE: To compare the performance of polyclonal fluorescence polarization immunoassay (pFPIA) with that of enzyme-multiplied immunoassay technique (EMIT) in patients receiving vancomycin and hemodialysis. SETTING: Outpatient hemodialysis center. PATIENTS: Seven subjects with end-stage renal disease treated with hemodialysis 3 times/week with a cellulose triacetate hemodialyzer. INTERVENTION: Subjects received vancomycin 1000 mg intradialytically during the first study session and 750 mg every other hemodialysis session thereafter for 4 weeks. MEASUREMENTS AND MAIN RESULTS: Blood samples were obtained throughout the study, and vancomycin serum concentrations were determined by pFPIA and EMIT. The mean +/- SD difference (estimate of bias) between assays was -1.10 +/- 1.35 mg/L. The limits of agreement (mean difference +/- 1.96 x SD) between them were -3.80-1.60 mg/L. CONCLUSION: Our data suggest that the manufacturer's changes in the vancomycin pFPIA eliminated overestimation of drug concentrations in patients undergoing high-permeability hemodialysis.

Anti-Bacterial Agents↗
PubMed1999

Vancomycin assay performance in patients with acute renal failure.

OBJECTIVE: Fluorescence polarization immunoassays (FPIA) have been reported to overestimate vancomycin serum concentrations compared to high-performance liquid chromatography (HPLC) or enzyme multiplied immunoassay technique (EMIT) in patients with chronic renal disease. The assay manufacturer has modified the FPIA to remedy this overestimation. The purpose of this study was to compare the assay performance of two FPIAs to EMIT in acute renal failure patients receiving vancomycin and continuous venovenous hemofiltration. DESIGN: Open-label trial. SETTING: Intensive care unit in a university affiliated hospital. PATIENTS AND PARTICIPANTS: 15 serum and ultrafiltrate samples were obtained from 14 critically ill patients (mean +/- SD; 57 +/- 12 years; 8 males/6 females). MEASUREMENTS AND RESULTS: Vancomycin concentrations were determined by a polyclonal FPIA (pFPIA) performed on the TDx system, a monoclonal FPIA (mFPIA) performed on the AxSYM system and EMIT. The coefficient of variation for all assays was < 5%. The mean difference +/- SDd between mFPIA vs EMIT and pFPIA vs EMIT assays in serum were: -0.08 +/- 1.55 and 1.24 +/- 2.11 mg/l, respectively. The limits of agreement between the mFPIA vs EMIT and pFPIA vs EMIT assays in serum were: -3.18 to 3.03 and -2.99 to 5.46 mg/l, respectively. CONCLUSIONS: Our data demonstrate that the manufacturer's changes to the pFPIA have reduced overestimation. The mFPIA appears to be an acceptable assay for measuring vancomycin serum concentrations in acute renal failure patients and does not significantly overestimate these concentrations.

Acute Kidney Injury↗
PubMed1999

Dialyzer-dependent changes in solute and water permeability with bleach reprocessing.

The effects of bleach reprocessing on the performance of high-flux dialyzers have not been comprehensively characterized. We compared the effects of automated bleach/formaldehyde reprocessing on solute and hydraulic permeability for cellulose triacetate (CT190) and polysulfone (F80B) dialyzers using an in vitro model. Dialyzers were studied after initial blood exposure (R0) and after 1 (R1), 5 (R5), 10 (R10), and 15 (R15) reuse cycles. Ultrafiltration coefficient (K(uf)), serial clearances, and/or sieving coefficients (SCs) of urea, creatinine, vancomycin, inulin, myoglobin, and albumin were determined. Urea, creatinine, and vancomycin clearances and SCs did not significantly differ from R0 to R15 with either dialyzer. Inulin clearances and SC also did not significantly change from R0 to R15 for the CT190. However, these same values for the F80B significantly increased (P < 0.05). The inulin clearance and SC values for the CT190 dialyzer were significantly higher than those for the F80B at all stages except R15. Myoglobin clearances significantly increased over 15 reuses for both dialyzers (P < 0.01). However, CT190 myoglobin clearances were significantly higher at all stages (R0 = 37.7 +/- 9.7; R15 = 52.5 +/- 8.8 mL/min) than the F80B (R0 = negligible; R15 = 41.3 +/- 16.5 mL/min; P < 0.01). Albumin pre- and postdialysis SCs significantly increased for both dialyzers (P < 0.01). K(uf) for R0 and R15 were 52.3 +/- 3.3 and 52.6 +/- 7.6 mL/h/mm Hg for CT190 (P = not significant) and 48.8 +/- 4.4 and 87.3 +/- 7.0 mL/h/mm Hg for F80B (P < 0.0001). We conclude that bleach reprocessing significantly increases larger solute and hydraulic permeability of high-flux cellulosic and polysulfone dialyzers. This effect is more pronounced for the polysulfone membrane. Until 10 reuses or greater, the removal of solutes greater than 1,500 d is significantly compromised with the polysulfone dialyzer used in this study.

Animals↗
PubMed1999

The effects of peracetic acid-hydrogen peroxide reprocessing on dialyzer solute and water permeability.

We characterized the effects of peracetic acid-hydrogen peroxide (PAHP) reprocessing on hemodialyzer permeability to water and solutes of various molecular weights and compared these effects within and between dialyzers. An aqueous-based solution containing urea, creatinine, vancomycin, inulin, myoglobin, and albumin was dialyzed for 60 minutes with a hemodialyzer after undergoing 0, 1 , 5, 10, and 15 reuse cycles. Solute clearance, sieving coefficient (SC), and ultrafiltration coefficient were determined. We found that PAHP reprocessing significantly decreased water and solute removal (urea, creatinine, vancomycin, inulin) by cellulose triacetate dialyzers (CT190) over 15 reuses (p<0.05) but did not affect the permeability of polysulfone dialyzers (F80A). Inulin removal was significantly lower for F80A than for CT190 (p<0.0001 and p<0.001 for clearance and SC values, respectively). Myoglobin and albumin removal by CT190 significantly decreased over 15 reuses (p<0.05), but no protein was detected in dialysate or ultrafiltrate at any reuse number for F80A. Reprocessing with PAHP alters dialyzer permeability; the effect is more pronounced for the CT190 dialyzer, but removal of solutes with molecular weight above 1500 Da is significantly lower with F80A dialyzers than with CT190. These changes in dialyzer permeability should be considered when determining optimal reuse procedures.

Creatinine↗
PubMed1999

Effect of gender on the pharmacokinetics of ofloxacin.

STUDY OBJECTIVES: To assess the influence of gender on the pharmacokinetics of ofloxacin. DESIGN: Open-label study. SETTING: Academic medical center. PATIENTS: Five healthy men and seven healthy women volunteers. INTERVENTIONS: Subjects received a single oral dose of ofloxacin 400 mg, and serial blood samples were collected for 24 hours. Plasma concentrations of ofloxacin were determined by high-performance liquid chromatography and pharmacokinetic parameters were determined. Statistical comparisons between genders were made with the Wilcoxon rank sum test. MEASUREMENTS AND MAIN RESULTS: Median volume of distribution at steady state/systemic bioavailability (V(ss)/F) was significantly smaller in women than in men, although when normalized for total body weight there were no differences. Except for terminal elimination half-life, which was 10% shorter in women, no other pharmacokinetic values were significantly different between genders. Median peak concentrations, although not statistically different, were 28% higher in women. CONCLUSION: Ofloxacin V(ss)/F values were smaller in women than in men, explained by gender-related differences in weight.

Administration, Oral↗
PubMed1997

Ticlopidine and aspirin therapy following implantation of coronary artery stents.

A number of studies evaluated the pharmacologic management of patients with coronary artery stents. Four studies demonstrated a low subacute thrombosis rate with antiplatelet therapy without implementation of anticoagulant therapy. However, in three of these trials conflicting results were reported regarding the relative efficacy of various antiplatelet therapies. Given the limitations of these studies, well-designed, randomized studies are necessary to assess the relative superiority of antiplatelet regimens to determine the safest and most effective treatment. Two clinical studies evaluated antiplatelet therapy compared with anticoagulant therapy in patients receiving coronary artery stents. Compared with conventional anticoagulant therapy, combined antiplatelet therapy with ticlopidine and aspirin appears to reduce clinical cardiovascular events, stent thrombosis, and hemorrhagic complications. Despite the potential benefits of therapy with ticlopidine observed in these studies, hematologic monitoring is required to detect neutropenia that may occur during ticlopidine therapy. In addition, the potential benefits of combination therapy with ticlopidine and aspirin apply only to patients at low risk as defined by the ACCP and ACC expert panels. Until further data become available, high-risk patients should be managed with conventional anticoagulation regimens. Studies are needed to determine whether antiplatelet therapy is effective in high-risk patients and the optimal antiplatelet therapy (ticlopidine, aspirin, or ticlopidine/aspirin) for the management of patients with coronary artery stents.

Angioplasty, Balloon, Coronary↗
PubMed1996

Racial differences in propranolol enantiomer kinetics following simultaneous i.v. and oral administration.

1. Racial differences in propranolol enantiomer kinetics following oral dosing were previously documented in our laboratory. The purpose of this study was to more completely describe propranolol kinetics in black and white subjects with the goal of gaining a better understanding of the mechanism(s) responsible for racial differences in oral propranolol kinetics. 2. Twelve white and 13 black healthy males were included in the study. Poor metabolizers of dextromethorphan and mephenytoin were excluded. Subjects took oral propranolol 80 mg every 8 h for 16 doses and received an intravenous dose of radiolabelled propranolol with the 16th dose. Serum and urine samples were collected for 24 h after the 16th dose. Serum concentrations of R- and S-propranolol and urine concentrations of its three primary metabolites were determined by h.p.l.c. 3. Apparent oral clearances of R- and S-propranolol were higher (P < 0.05) in blacks than whites (R-propranolol: 5036 +/- 4175 ml min-1 vs 2854 +/- 879 ml min-1; S-propranolol 3255 +/- 1723 ml min-1 vs 2125 +/- 510 ml min-1; blacks vs whites). 4. R- and S-propranolol clearances were higher in blacks than whites (R-propranolol 1069 +/- 316 ml min-1 vs 841 +/- 161 ml min-1; S-propranolol 947 +/- 271 ml min-1 vs 771 +/- 142 ml min-1; blacks vs whites, P < 0.05). 5. There were trends (P > 0.05 < 0.10) toward higher side chain oxidation, 4-hydroxylation and R-propranolol glucuronidation in blacks compared with whites. Ethnic differences in the enantiomeric ratios of partial metabolic clearance values were not observed. 6. We conclude the higher propranolol oral clearances in black subjects are explained by blacks having slightly higher hepatic metabolism via all three of its major metabolic pathways. Higher propranolol clearances among black subjects were also observed and we conclude this finding is explained largely by the higher hepatic metabolism, but also by slightly higher liver blood flow among black subjects.

Administration, Oral↗
PubMed1995

Effect of aging on atenolol pharmacokinetics and pharmacodynamics.

A study was conducted to characterize and compare the pharmacodynamics and pharmacokinetics of atenolol in young and elderly men. Six young (mean +/- SD, 25.0 +/- 3.0 years) and six elderly (63.0 +/- 3.2 years) healthy men took atenolol 100 mg orally once daily for 6 days. Heart rate response to submaximal exercise was measured at selected times for 48 hours, and plasma and urine samples were collected over the same time interval. The Sigmoid Emax model was fit to percent reductions in exercise heart rate and atenolol plasma concentrations. The younger men had significantly lower values for area under the steady-state plasma concentration-time curve and higher values for systemic clearance/F and renal clearance. EC50 values showed a trend toward greater sensitivity to the negative chronotropic effects of atenolol among the elderly men. Model-derived percent reductions in heart rate were greater at all concentrations among the elderly men. These data suggest that group differences in atenolol pharmacokinetics were likely a result of age-related decline in renal function, and that the elderly subjects were at least as sensitive as, and maybe even more sensitive than, the younger subjects to the negative chronotropic effects of atenolol.

Adrenergic beta-Antagonists↗
PubMed1995

Racial differences in sensitivity to the negative chronotropic effects of propranolol in healthy men.

OBJECTIVE: Dose-response studies in patients with hypertension have shown that black subjects are less responsive to beta-blocker therapy than white subjects, whereas studies in healthy volunteers suggest marginal or no racial differences in response. No concentration-response studies have been conducted in black subjects and white subjects. The purpose of this study was to characterize beta-blocker pharmacodynamics in healthy black and white men. METHODS: Thirteen black and 13 white healthy men took 80 mg oral propranolol three times daily, for a total of 16 doses. Heart rate response to treadmill exercise was measured at various times over 24 hours. Serum propranolol samples were collected during the same 24-hour time period and were measured by chiral HPLC. The sigmoid maximal effect (Emax), Emax, and linear models were fitted to percentage reductions in exercise heart rate and S-propranolol concentrations. RESULTS: Black subjects had significantly lower values for serum concentration producing one-half the maximal effect (EC50) and unbound EC50 than white subjects (EC50: 10.2 ng/ml (4.4 to 28.0 ng/ml) versus 24.4 ng/ml (14.3 to 64.1 ng/ml), blacks versus whites; unbound EC50: 1.29 ng/ml (0.686 to 4.91 ng/ml) versus 2.77 ng/ml (1.70 to 8.11 ng/ml), blacks versus whites). There was no statistical difference in Emax (33.3% [22.2% to 39.7%] versus 38.3% [30.7% to 45.1%], blacks versus whites). CONCLUSIONS: Healthy black men were more sensitive to beta-blockade than healthy white men. The results of this study in healthy volunteers suggest that the racial differences in response observed in patients with hypertension are related to hypertensive pathophysiology rather than normal physiology.

Adult↗
PubMedDate not supplied

Small and middle molecular weight solute clearance in nocturnal intermittent peritoneal dialysis.

OBJECTIVES: To determine the dialysate-to-plasma (D/P) concentration ratios and peritoneal dialytic clearance (CI(D)) of substances with a wide range of molecular weights in subjects receiving a simulated nocturnal intermittent peritoneal dialysis (NIPD) session. DESIGN: Open-label single-dose study. SUBJECTS: Six end-stage renal disease patients undergoing peritoneal dialysis (PD). SETTING: Clinical research center of a university-affiliated hospital. INTERVENTIONS: Subjects received intravenous gentamicin and vancomycin on the first day of the study. Subjects received no PD until their return on the following day, when subjects underwent a simulated NIPD session utilizing four 2- to 2.5-L peritoneal dialysate dwells of 2 hours. Blood and dialysate samples were collected immediately before the session and after each dialysate dwell for determination of urea, creatinine, gentamicin, vancomycin, and beta2-microglobulin (beta2M) concentrations. Each solute's D/P concentration ratio and peritoneal CI(D) were calculated. MEASUREMENTS AND MAIN RESULTS: The (mean +/- SD) 2-hour D/P concentration ratios were 0.78 +/- 0.05 (urea), 0.49 +/- 0.11 (creatinine), 0.38 +/- 0.08 (gentamicin), 0.11 +/- 0.06 (vancomycin), and 0.07 +/- 0.03 (beta2M). Peritoneal CI(D) values (mL/min of dialysis) were 19.0 +/- 2.8 (urea), 12.1 +/- 3.5 (creatinine), 8.4 +/- 2.8 (gentamicin), 2.7 +/- 1.5 (vancomycin), and 1.7 +/- 0.8 (beta2M). The D/P concentration ratios and peritoneal CI(D) values for urea, creatinine, and gentamicin were significantly different from vancomycin and beta2M (repeated measures ANOVA, p < 0.05). Beta2-microglobulin peritoneal CI(D) was strongly related to gentamicin peritoneal CI(D) (r = 0.96, p < 0.05). CONCLUSION: Small molecular weight solutes have significantly greater D/P and peritoneal CI(D) than middle molecular weight solutes in NIPD. In NIPD, daily peritoneal CI(D) of beta2M is lower than that reported in continuous ambulatory PD. NIPD also results in lower drug CI(D) than that reported in continuous ambulatory PD studies.

Adult↗