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R F Frye

Publications and source records attributed to R F Frye.

43 records · Page 3Linked to original sources
PubMed1993

Sensitive high-performance liquid chromatographic determination of chlorzoxazone and 6-hydroxychlorzoxazone in plasma.

A rapid and sensitive high-performance liquid chromatographic assay was developed for the quantitation of chlorzoxazone and its major metabolite 6-hydroxychlorozoxazone in plasma. These compounds, as well as the internal standard 5-fluorobenzoxazolone, were extracted from plasma (0.5 ml) using C18 solid-phase extraction columns. The extracts were analyzed on a 10-microns Waters C18 muBond-apak column with a mobile phase of acetonitrile-tetrahydrofuran-0.1 M ammonium acetate (22.5:5.5:72). The assay utilized ultraviolet detection (283 nm) which provided sensitivity and specificity sufficient to simultaneously quantify > or = 100 ng/ml chlorozoxazone and 6-hydroxychlorzoxazone in plasma. The mean correlation coefficient of the multi-level standard curves for each compound was 0.996 or greater over a concentration range of 100-3000 ng/ml. The inter-day and intra-day coefficients of variation were < 6%. This method has been used by our laboratory to provide the unattended overnight analysis of chlorozoxazone and 6-hydroxychlorzoxazone in plasma samples obtained from human study subjects.

Calibration↗
PubMed1993

Estimation of the hepatic extraction ratio of indocyanine green in swine.

1. The hepatic extraction ratio of Indocyanine Green was measured directly by trans-hepatic catheterization in 14 outbred swine (eight well-fed, six malnourished). A specific two-compartment pharmacokinetic model was fitted to the arterial Indocyanine Green concentration-time data and used to estimate the hepatic extraction ratio of Indocyanine Green. 2. The specific two-compartment pharmacokinetic model was modified to represent more accurately the physiological process of Indocyanine Green removal. Simulations were performed using this new model to estimate the hepatic extraction ratio of Indocyanine Green in the swine. 3. Similarly to previous findings, our data showed that the original model consistently overestimated the hepatic extraction ratio of Indocyanine Green (i.e. the model estimate was compared with the true, directly measured value). 4. The comparison of the modified model and the original model clearly indicates the reason for the overprediction of the hepatic extraction ratio of Indocyanine Green by the latter. The simulations using the new model indicate that the percentage of binding of Indocyanine Green to its transport protein (glutathione S-transferase) for removal in the bile will affect the estimation of the hepatic extraction ratio of Indocyanine Green. Thus, the amount of Indocyanine Green available for removal is less than that assumed by the original model.

Animals↗
PubMed1992

Teicoplanin nephrotoxicity: first case report.

A 71-year-old man with type I diabetes mellitus was admitted to the hospital for the treatment of osteomyelitis of the left great toe secondary to methicillin-resistant Staphylococcus aureus. The patient was enrolled in an investigational protocol and was treated with teicoplanin 1200 mg/day. Following 40 days of treatment, the patient developed both markedly elevated serum creatinine and blood urea nitrogen. Urine analysis also showed the presence of protein. The eosinophils were markedly elevated in the blood. The patient was subsequently diagnosed with a probable drug-induced acute interstitial nephritis. Treatment with furosemide and hemodialysis over the next two weeks failed to produce improvement in renal function. The patient was referred for long-term dialysis. The data presented in this report suggest the possible relationship of teicoplanin and the development of renal failure in this patient. Periodic monitoring of renal function and follow-up are probably warranted in patients receiving long-term teicoplanin therapy.

Aged↗
PubMedDate not supplied

Pharmacokinetics of intermittent intraperitoneal cefazolin in continuous ambulatory peritoneal dialysis patients.

OBJECTIVE: To investigate the pharmacokinetic parameters of intermittent intraperitoneal (IP) cefazolin, and recommend a cefazolin dosing regimen in continuous ambulatory peritoneal dialysis (CAPD) patients. DESIGN: Prospective nonrandomized open study. SETTING: CAPD outpatient clinic in Albany, New York. PATIENTS: Seven volunteer CAPD patients without peritonitis. Three of the patients were nonanuric while 4 were anuric. INTERVENTIONS: Cefazolin (15 mg/kg total body weight) was given to each patient during the first peritoneal exchange. Blood and dialysate samples were collected at times 0, 0.5, 1,2,3,6 (end of the first antibiotic-containing dwell), 24, and 48 hours after the administration of IP cefazolin. Urine samples were collected in nonanuric patients over the study period. RESULTS: The mean+/-SD amount of cefazolin dose absorbed from the dialysate after the 6-hour dwell was 69.7%+/-8.0% of the administered dose. The cefazolin absorption rate constant from dialysate to serum was 0.21+/-0.1/hr (absorption half-life 3.5+/-0.8 hr). The mean serum concentrations reached at 24 and 48 hours were 52.4+/-3.7 mg/L and 30.3+/-5.9 mg/L, respectively. The mean dialysate cefazolin concentrations reached at 24 and 48 hours were 15.1+/-3.4 mg/L and 7.9+/-1.4 mg/L, respectively. The cefazolin serum elimination rate constant was 0.02+/-0.01/hr (elimination half-life 31.5+/-8.8 hr). The total cefazolin body clearance was 3.4+/-0.6 ml/min. In the 3 nonanuric patients the mean renal clearance of cefazolin was 0.6+/-0.4 ml/min. The peritoneal clearance of cefazolin was 1.0+/-0.3 mL/min. The systemic volume of distribution of cefazolin was 0.2+/-0.05 L/kg. No statistical difference was detected in pharmacokinetic parameters between anuric and nonanuric patients, although this may be due to the small number of patients in each group. CONCLUSION: A single daily dose of cefazolin dosed at 15 mg/kg actual body weight in CAPD patients is effective in achieving serum concentration levels greater than the minimum inhibitory concentration for sensitive organisms over 48 hours, and dialysate concentration levels over 24 hours. Caution is warranted in extrapolation of dosing recommendations to patients who maintain a significant degree of residual renal function.

Absorption↗
PubMedDate not supplied

Intravenous vancomycin pharmacokinetics in automated peritoneal dialysis patients.

The pharmacokinetics of intravenous (i.v.) vancomycin was studied in automated peritoneal dialysis (APD) patients who received a single i.v. dose of vancomycin (15 mg/kg total body weight). Dialysate samples were collected at the beginning, middle, and end of dwells 1-3 (on-cycler), and at the end of dwells 4 and 5 (off-cycler), for a 24-hour period. Blood samples were collected at the beginning, middle, and end of dwells 1-3 (on-cycler), and at the end of dwell 5 (off-cycler) for a 24-hr period. Pharmacokinetics parameters were calculated assuming a one-compartment model. Glomerular filtration rate (GFR) and vancomycin clearance (CI) values were normalized to 1.73 m2. Ten patients [4 males, 6 females; 47.4 +/- 9.9 years of age (mean +/- SD)] who had received PD for a median 3.5 months (range 2-66 months) were studied. Dwell times were 2.3 +/- 0.1 hours on cycler and 7.3 +/- 0.1 hours off cycler. Vancomycin half-life was significantly different on-cycler than off-cycler (11.6 +/- 5.2 hr vs 62.8 +/- 33.0 hr; p < 0.001). Vancomycin total CI (CI(T)) was 7.4 +/- 2.0 mL/min. Renal CI (CI(R)) and PD CI (CI(PD)) accounted for 23.6% and 28.0% of CI(T). respectively. CI(R) correlated with GFR (CI(R) = 0.90 GFR - 1.01; r2 = 0.79; p = 0.008). Mean vancomycin serum and dialysate end-of-dwell concentrations were above minimum inhibitory concentration of susceptible organisms (5 micro/mL) for the first cycler and the second ambulatory exchanges only. The results of this study suggest that, to provide adequate concentrations for susceptible organisms over a 24-hour period, current intermittent vancomycin dosing recommendations for PD-related peritonitis need to be changed to 35 mg/kg intraperitoneally on day 1, then 15 mg/kg i.p. thereafter (i.e., once daily) in APD patients.

Adult↗