Pharmacokinetics ? Uses and abuses

Fell, Patrick J.; Stevens, M

doi:10.1007/bf00567122

Cited by 22 publications

(8 citation statements)

References 19 publications

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“…In our experience, estimates of the parameters can be extremely unreliable under certain conditions. A major factor influencing the error in parameter estimation is the number of sampling points and their timing (Fell & Stevens, 1975). In our study 17 plasma samples were collected over 10.5 h, the corresponding figure in the study of Dalhoff et al (1981) was 18 samples over 6 h. Although our figure must be regarded as frequent sampling, there are only 17 -6 = 11 degrees of freedom left for the estimation of the six parameters.…”

Section: Discussionmentioning

confidence: 73%

Renal excretion of intravenously infused amoxycillin and ampicillin.

Sjövall¹,

Westerlund²,

Alván³

1985

Brit J Clinical Pharma

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1 The aim of this study was to determine whether concentration-dependent renal clearance of ampicillin and amoxycillin occurs. The drugs were given as single 20 min i.v. infusions in doses ranging from 1.9 to 2.8 g to nine healthy volunteers using a cross-over design. 2 Plasma and urinary concentrations were determined by a selective liquid chromatographic method using frequent sampling up to 10 and 30 h respectively after termination of the infusion. The renal clearance of the drugs was independent of the plasma concentration. The mean (s.d.) renal clearances of ampicillin and amoxycillin were 167 (24) and 157 (20) ml min-' 1.73 m-2 respectively. The net secretion was about 50% of the total renal clearance of both drugs. 3 The plasma concentration and urinary excretion rate versus time curves indicated a polyexponential decline, which could be described by both a biexponential and a triexponential equation. The former proved to be more reliable, especially in the calculation of micro rate constants. There was a tendency to more sustained plasma concentrations after amoxycillin, also illustrated by a significantly lower mean (s.d.) plasma clearance of this drug, viz. 185 (30) ml min-1 1.73 m-2, as compared to ampicillin, 210 (24) ml min-' 1.73 m-2 (P < 0.04). 4 There were no major differences in the disposition rate constants and the distribution volumes of ampicillin and amoxycillin. The mean (s.d.) plasma half-life was 1.7 (0.3) h for both drugs. The urinary excretion rate indicated a slower terminal disposition rate however, with ampicillin and amoxycillin half-lives of 3.4 (2.0) and 3.9 (1.2) h respectively. The longer half-life in the terminal phase may be due to increased tubular reabsorption at low urinary concentrations. It was not possible to determine in this study whether the half-life was affected by changes in clearance or volume of distribution. 5 The urinary solubility of the drugs was dependent on pH. This could explain the massive macroscopic crystalluria seen in one subject after amoxycillin. Three hours after termination of the infusion, crystals could no longer be found in the sediment. There was no clinical or laboratory evidence of renal damage.

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Section: Discussionmentioning

confidence: 73%

Renal excretion of intravenously infused amoxycillin and ampicillin.

Sjövall¹,

Westerlund²,

Alván³

1985

Brit J Clinical Pharma

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“…July 1978 pharmacokinetic study. 7,9 In the earlier study, plasma was sampled for no more than 2.5 hr after termination of morphine infusion. It is not surprising that kinetic analysis of those plasma levels yielded shorter elimination half-lifes and smaller apparent volumes of distribution than in this investigation in which analysis was based upon 18 hr samplings.…”

Section: Discussionmentioning

confidence: 99%

Kinetics of intravenous and intramuscular morphine

Stanski

Greenblatt

Lowenstein

1978

Clin Pharma and Therapeutics

227

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The disposition of parenteral morphine was assessed in two pharmacokinetic studies. In Study 1, 10 mg of morphine sulfate was administered by intravenous (IV) infusion, intramuscular (IM) injection, or both, to 8 healthy young adult male volunteers. Plasma morphine concentrations were determined by radioimmunoassay in multiple blood samples drawn after each dose. Mean (+/-SE) kinetic parameters following IV morphine were: volume of distribution (Vd), 3.2 (+/- 0.3) L/kg; elimination half-life (t1/2beta), 2.9 (+/- 0.5) hr; clearance, 14.7 (+/- 0.9) ml/min/kg; extraction ratio, 0.70 (+/- 0.04). After IM morphine, peak plasma levels ranged from 51 to 62 ng/ml and were reached within 20 min of injection. The absorption half-life averaged 7.7 (+/- 1.6) min. Systemic availability was 100% complete. In study 2, 4 elderly male patients (61 to 80 yr of age) received 45 to 80 mg of morphine sulfate IV prior to operative repair of an abdominal aortic aneurysm. Morphine pharmacokinetics were determined as described above. Kinetic variables were Vd, 4.7 (+/- 0.2) L/kg; t1/2beta, 4.5 (+/- 0.3) hr; clearance, 12.4 (+/- 1.2) ml/min/kg; extraction ratio, 0.59 (+/- 0.05). Both studies demonstrate that morphine distribution is rapid and extensive and its t1/2beta relatively short. IM morphine is rapidly and completely absorbed.

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“…This illustrates the difficulty of drawing quantitative conclusions from the rate constants obtained from multicompartmental models. This has been stressed in a recent review article (Fell & Stevens, 1975).…”

Section: Renal Clearancementioning

confidence: 95%

“…The standard deviations of the parameters shown in Table 2 (Fell & Stevens, 1975 The time honoured practice of giving repeated small doses of digoxin during digitalisation may not be necessary. The total oral loading dose could be given at the start of therapy, followed thereafter by the appropriate maintenance dose.…”

Section: Interpretation Of the Three Compartmental Modelmentioning

confidence: 99%

Digoxin pharmacokinetics: multicompartmental analysis and its clinical implications.

Sumner¹,

Russell²

1976

Brit J Clinical Pharma

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1 The kinetics of digoxin have been investigated in healthy volunteers using an isotopic tracer technique. 2 A three compartment open kinetic model has been proposed as the simplest model consistent with the plasma, urinary and faecal data obtained. 3 The renal clearance of digoxin (mean ± s.d.) was found to be 119 ± 10 ml/min, which did not differ significantly from the glomerular filtration rate (1 10 ± 14 ml/min). 4 Digoxin extra-renal clearance (mean ± s.d.) was found to be 47 ± 7 ml/min. 5 The model predicts that the tissue concentration attained after four 0.25 mg oral doses spread over 24 h can be achieved within a period of 4 h following a single oral loading dose of 1 mg.6 Maintenance doses can be derived from a simple formula based on the glomerular filtration rate, extra-renal clearance and bioavailability of the digoxin preparation used.

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Pharmacokinetics ? Uses and abuses

Cited by 22 publications

References 19 publications

Renal excretion of intravenously infused amoxycillin and ampicillin.

Renal excretion of intravenously infused amoxycillin and ampicillin.

Kinetics of intravenous and intramuscular morphine

Digoxin pharmacokinetics: multicompartmental analysis and its clinical implications.

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