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  • 1
    Electronic Resource
    Electronic Resource
    Ranitidine pharmacokinetics in continuous ambulatory peritoneal dialysis (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 587-591 
    Details
    ISSN: 1432-1041
    Keywords: ranitidine ; dialysis ; H2-receptor antagonist ; continuous ambulatory peritoneal dialysis ; renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ranitidine kinetics in renal failure were evaluated in six patients undergoing continuous ambulatory peritoneal dialysis (CAPD). On separate occasions each patient received either 50 mg intravenously (i.v.) or 150 mg orally of ranitidine HCl. Following i.v. administration, the plasma concentration vs time curve was best described by a two compartment model with firstorder elimination. The mean ± SD distribution and elimination rate constants were 2.47±0.78 and 0.098±0.013 h, respectively. The area under the serum concentration vs time curve after the i.v. dose was 5979±2870 μg·h· 1−1, resulting in a mean volume of distribution of 76.81 and a total body clearance of 126 ml·min−1. Following oral administration the observed maximum plasma concentration was 904±483 μg·l−1 at 4.2±1.8 h, and the bioavailability was 69.7±35.6%. The peritoneal clerance of ranitidine was 3.2±0.7 and 2.6±0.6 ml·min−1 for the i.v. and oral groups, respectively. The amount of drug removed by dialysis was 561.2±336.2 μg for the i.v. and 1197.1±602.3 μg for the oral group. Four patients in the i.v. group had urine output during the study period with renal ranitidine clearance values of 9.9±9.9 ml· min−1. Two patients in the oral group had urine output and corresponding renal ranitidine clearance values of 5.1 and 20.1 ml·min−1. A dosage regimen for ranitidine is proposed based on ranitidine kinetics in patients undergoing CAPD.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02455993
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  • 2
    Electronic Resource
    Electronic Resource
    Fosinopril pharmacokinetics and pharmacodynamics in chronic ambulatory peritoneal dialysis patients (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 165-169 
    Details
    ISSN: 1432-1041
    Keywords: Fosinopril ; fosinoprilat ; CAPD ; ACE-inhibitor ; pharmacokinetics ; pharmacodynamics ; peritoneal dialysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and pharmacodynamics of fosinoprilat, the diacid of fosinopril sodium, a new angiotensin-converting enzyme (ACE) inhibitor, were investigated after the oral administration of 10 mg of fosinopril sodium to 6 chronic ambulatory peritoneal dialysis (CAPD) patients. The results from 1 patient are reported separately because of the presence of concomitant liver dysfunction. The mean t1/2, Cmax, tmax, and AUC values for 5 of the CAPD patients were 19.5 h, 202 ng·ml−1, 4.8 h, and 3.19 μg·h·ml−1, respectively. Values for 1 CAPD patient with liver dysfunction were t1/2 of 65.4 h, Cmax of 182 ng·ml−1, tmax of 9 h, and AUC of 18.1 μg·h·ml−1. Peritoneal clearance of fosinoprilat was negligible, ranging from 0.07 to 0.23 ml·min−1. Serum ACE activity remained significantly suppressed at 24 and 48 h after fosinopril sodium administration with mean decreases from baseline of 94.2% and 70.6%, respectively. ACE activity was suppressed to an even greater degree in the patient with liver dysfunction, remaining 97% inhibited 72 h after drug administration. Plasma renin activity (PRA) increased and plasma aldosterone concentrations decreased following drug administration. Mean arterial pressure did not change appreciably throughout the study. Dosage reductions may not be necessary in the majority of dialysis patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265911
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  • 3
    Electronic Resource
    Electronic Resource
    The pharmacokinetics of carvedilol and its metabolites after single and multiple dose oral administration in patients with hypertension and renal insufficiency (1999)
    Springer
    European journal of clinical pharmacology 55 (1999), S. 269-277 
    Details
    ISSN: 1432-1041
    Keywords: Key words Carvedilol ; Hypertension ; Renal insufficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Introduction: Carvedilol, a chiral compound possessing nonselective β- and α1-blocking activity, is used for the treatment of hypertension and congestive heart failure (CHF). The enantiomers of carvedilol exhibit similar α1-blocking activity; only S-carvedilol possesses β-blocking activity. Carvedilol is primarily hepatically metabolized, with less than 2% of the dose excreted renally as unchanged drug. Methods: The pharmacokinetics of carvedilol, R-carvedilol, and S-carvedilol were studied in hypertensive patients (control; n = 13) versus patients with hypertension and advanced renal insufficiency not yet on dialysis [GFR ≤ 30 ml · min−1 (CRI, chronic renal insufficiency), n = 12] following single (12.5 mg, Day 1) and multiple (25 mg once daily, Days 2–9) dosing. Results: Mean with (SD) AUC(0–24h) (ng · h · ml−1) for carvedilol was 220 (120) and 618 (335) in CRI compared with 165 (83.5) and 413 (247) in controls on Days 1 and 9, respectively, primarily due to higher R-carvedilol concentrations. Mean with (SD) Cmax (ng · ml−1) for carvedilol were 53.4 (31.4) and 128 (63.3) in CRI compared with 46.7 (23.3) and 104 (58.9) in controls on Days 1 and 9, respectively. The difference in group mean values was characterized by considerable overlap in individual AUC(0–24h) and Cmax values between groups. There was no apparent difference in mean terminal elimination half-life for carvedilol between groups on each study day. Less than 1% of the dose was excreted in urine as unchanged carvedilol in both groups. Blood pressure and heart rate declined in both groups to a similar degree. Conclusion: Compared with controls, average AUC(0–24 h) values for carvedilol were approximately 40% and 50% higher on study Days 1 and 9 in patients with renal insufficiency, primarily due to higher R-carvedilol concentrations with only a small change (〈20%) in S-carvedilol concentrations, the isomer possessing β-blocking activity. These changes in pharmacokinetics are modest in view of the large interindividual variability. Carvedilol was well tolerated in both groups. Although the present study cannot provide a final conclusion, based on the results of the present study, no changes in dosing recommendations for carvedilol are warranted in patients with moderate/severe renal insufficiency.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050628
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  • 4
    Electronic Resource
    Electronic Resource
    Cefmenoxime kinetics during continuous ambulatory peritoneal dialysis (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 713-717 
    Details
    ISSN: 1432-1041
    Keywords: cefmenoxime ; peritoneal dialysis ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of the aminothiazolyliminomethoxy cephalosporin, cefmenoxime, were determined after a 30 min intravenous infusion of 15 mg/kg body weight in 6 adult subjects undergoing continuous ambulatory peritoneal dialysis. Concentrations of cefmenoxime in serum, urine and dialysate were determined by high-pressure liquid chromatography. The mean peak serum concentration was 92.8±11.6 µg/ml and the harmonic mean for the elimination half-life was 5.46 h. The volume of distribution at steady-state was 14.60±3.01 l/kg. Total body clearance of the drug was 31±7.7 ml/min with 8±5% and 5.75±2.72% of the administered dose being eliminated by renal and peritoneal clearance, respectively. Peritoneal clearance for all exchanges (n=24) was 1.93±68 ml/min. These data suggest that peritoneal losses of this drug are minimal and doses conventionally employed in advanced renal failure can be utilized in the management of systemic infections.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00608221
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  • 5
    Electronic Resource
    Electronic Resource
    The pharmacokinetics and pharmacodynamics of fosinopril in haemodialysis patients (1993)
    Springer
    European journal of clinical pharmacology 45 (1993), S. 431-436 
    Details
    ISSN: 1432-1041
    Keywords: Fosinopril ; ACE inhibitors ; haemodialysis ; pharmacokinetics ; pharmacokinetics-pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and pharmacodynamics of fosinoprilat, the diacid of fosinopril sodium (a new angiotensin-converting enzyme (ACE) inhibitor), were investigated in six haemodialysis patients. Intravenous 14C-fosinoprilat (7.5 mg), oral 14C-fosinopril sodium (10 mg) and oral fosinopril sodium (10 mg) were administered in an open-label, randomized study. Mean maximum concentration (Cmax), clearance (CL), volume of distribution at steady-state (Vss), mean residence time (MRTiv), and t1/2 values after IV administration of 14C-fosinoprilat were 2,042 μg·ml−1, 11.3 ml·min−1, 11.01, 16.3 h and 28.3 h, respectively. Following oral administration of 14C-fosinopril, mean Cmax, time to maximum plasma concentration (tmax), and fosinoprilat bioavailability values were 197 ng·ml−1, 5.2 h and 29.2 %. Para-hydroxy fosinoprilat and fosinoprilat glucuronide comprised approximately 15 % and 2 % of radioactivity recovered in faeces. Four hours of haemodialysis only cleared approximately 1.5 % of the administered dose. The maximum effect (Emax) model was fitted to the percentage inhibition of serum ACE activity vs. fosinoprilat concentration data in three patients. Emax ranged from 95.3 to 102.5 %, and IC50 (the fosinoprilat concentration required to produce 50 % of Emax) ranged from 2.6 to 4.2 ng·ml−1. Pharmacokinetic variables of the patients were similar to those in patients with moderate to severe renal dysfunction. Dosage modifications or supplemental dosing following dialysis are unnecessary.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315514
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  • 6
    Electronic Resource
    Electronic Resource
    The pharmacokinetics of pravastatin in patients on chronic hemodialysis (1997)
    Springer
    European journal of clinical pharmacology 53 (1997), S. 117-121 
    Details
    ISSN: 1432-1041
    Keywords: Key words Pravastatin ; Hemodialysis; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The single-dose and steady-state pharmacokinetics of the HMG CoA reductase inhibitor pravastatin and its two metabolites, SQ 31 906 and SQ 31 945, were evaluated in 12 hemodialysis patients. A single 20-mg i.v. dose was employed, followed by daily oral dosing of 20 mg over four hemodialysis intervals. Results: No statistical differences in the pharmacokinetics of pravastatin or SQ 31 906 were evident when comparing the first and last days of oral dosing with pravastatin. The pharmacokinetic parameters of pravastatin and SQ 31 906 were similar to those of healthy volunteers. SQ 31 945, the inactive polar metabolite, did accumulate in dialysis patients, as evidenced by an accumulation index of 1.7 ± 1.0. Although metabolic clearance is the predominant mode of elimination of pravastatin, hemodialysis clearances of pravastatin, SQ 31 906 and SQ 31 945 will contribute to total body clearance since dialytic clearance ranged from 40 to 80 ml · min−1. Conclusion: Pravastatin can be safely administered in the usual dosages to subjects with renal failure on hemodialysis and no change in dosing is necessary.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050348
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  • 7
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and protein binding of methocarbamol in renal insufficiency and normals (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 193-194 
    Details
    ISSN: 1432-1041
    Keywords: methocarbamol ; haemodialysis ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We determined plasma methocarbamol concentrations over 24 h following a 1.5 g methocarbamol dose (off-dialysis day) to 8 chronic haemodialysis patients and compared these results to those from 17 healthy male volunteers. The harmonic mean elimination half-life was similar between the two groups, 1.24 and 1.14 h, respectively. tmax and the weight-adjusted Cmax were 1.1 h and 27.0 mg · m−1 for haemodialysis patients and 1.1 and 23.1 mg · l−1 for normals. Relative systemic availability was assessed by comparing weight-normalized AUC × k10 products. These results indicate no significant differences with respect to methocarbamol absorption, with the relative systemic availability in patients being 113%. These data suggest that absorption and elimination of methocarbamol is similar between normal subjects and patients undergoing maintenance haemodialysis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00280060
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