Liquid-chromatographic measurement of endogenous and exogenous glucocorticoids in plasma.

Frey, F J; Frey, B M; Benet, Leslie Z.

doi:10.1093/clinchem/25.11.1944

Cited by 100 publications

(13 citation statements)

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“…All plasma samples were analyzed for prednisolone and prednisone by a HPLC procedure (22). The intraday variability coefficient of variation; (CV) of the method was 1 to 4% and the interday CV was 2.8 to 10.6% (22). Equilibrium dialysis was performed to quantify the concentration of unbound prednisolone in plasma (23).…”

Section: Methodsmentioning

confidence: 99%

Impaired liver function in stable renal allograft recipients

et al. 1989

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Hepatic failure as a cause of death is increased in stable renal allograft recipients when compared with patients on dialysis. In order to assess the magnitude and the natural history of the hepatic functional derangement, the kinetics of xenobiotics which are metabolized by cytosolic (galactose) or microsomal (prednisolone, cyclosporine A) enzymes were determined in 28 consecutive stable kidney transplant patients 1 month and 1 year after transplantation. Renal transplant patients had a decreased mean (+/- S.D.) galactose elimination capacity at 1 month (6.26 +/- 0.94 mg per min x kg) and at 1 year (5.93 +/- 0.96 mg per min x kg), when compared with a different group of 28 healthy control subjects (7.52 +/- 0.78 mg per min x kg, p less than 0.001) and a decreased total body clearance of prednisolone at 1 month (2.13 +/- 0.34 ml per min x kg vs. 2.71 +/- 0.43 ml per min x kg in controls, p less than 0.001), which further decreased over the following year to 1.76 +/- 0.32 ml per min x kg (p less than 0.001). The clearance of cyclosporine A declined significantly during the first year of successful transplantation (5.9 +/- 2.1 ml per min x kg vs. 4.9 +/- 1.2 ml per min x kg, p less than 0.05). In conclusion, a substantial proportion of stable renal transplant recipients have decreased cytosolic and microsomal liver functions despite the absence of clinical and laboratory evidence of significant liver disease.

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Section: Methodsmentioning

confidence: 99%

Impaired liver function in stable renal allograft recipients

et al. 1989

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“…method. Samples were prepared for analysis using the method of Frey et al (1979). Chromatography was carried out using a model M-6000A pump and model 450 u.v.…”

Section: Methodsmentioning

confidence: 99%

Alterations in prednisolone disposition as a result of time of administration, gender and dose.

Meffin¹,

Brooks²,

Sallustio³

1984

Brit J Clinical Pharma

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1 The disposition of total and free prednisolone has been studied in four male and four female volunteers, each of whom received an intravenous dose of 0.075 mg/kg (low) and 1.5 mg/kg (high) of prednisolone at both 06.00 h and 18.00 h. 2 For the low dose, free prednisolone clearance was 14% lower (P = 0.012) and time-averaged prednisolone free fraction was 22% higher (P < 0.001) in the morning, there being no circadian difference in total prednisolone clearance. There was no circadian differences in prednisolone disposition at the high dose. These findings are consistent with a mechanism in which cortisol causes a simultaneous competitive inhibition of prednisolone clearance and plasma protein binding at low, but not at high prednisolone doses. 3 Prednisolone clearance was higher in female than in male subjects, the mean increase being 18% (P = 0.022) for total prednisolone and 21% (P = 0.036) for free prednisolone. 4 Mean total prednisolone clearance and steady-state distribution volume were two-fold higher at the high vs the low dose (P < 0.001), but free prednisolone clearance showed a dose dependent decrease of 11% (P = 0.019). There was no change in free prednisolone steady-state distribution volume.

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“…All plasma samples and the urine were analysed for prednisolone by a high performance liquid chromatographic procedure [4]. Briefly, the steroids, along with an internal standard, dexamethasone, are extracted from 1 ml of plasma or urine with methylene chlorideether, washed with acid, base and distilled water.…”

Section: Methodsmentioning

confidence: 99%

“…Due to non-linear binding of prednisolone to albumin and transcortin, the total and unbound concentrations in the lymphocyte cultures (see below) following dilution of the plasma samples with culture 2.8-10.6% [4]. medium (1: 1, v/v) had to be calculated for each plasma sample as described recently [7].…”

Section: Methodsmentioning

confidence: 99%

Phenytoin modulates the pharmacokinetics of prednisolone and the pharmacodynamics of prednisolone as assessed by the inhibition of the mixed lymphocyte reaction in humans

Frey

1984

Eur J Clin Investigation

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Following induction of the microsomal liver enzymes, lower total prednisolone concentrations in plasma and an altered pattern of the prednisolone metabolites generated were observed. The purpose of the present study was to establish whether--as a consequence of an enhanced clearance--lower unbound concentrations of prednisolone in plasma are detectable after enzyme induction and to determine if the altered prednisolone metabolism modulates the biological effect. Before and during phenytoin dosage in ten volunteers, the mean (+/-SD) total body clearance (ml min-1 kg-1) of both total and unbound prednisolone increased from 2.74 +/- 0.47 to 3.94 +/- 0.66 (P less than 0.001) and from 10.76 +/- 2.68 to 16.00 +/- 3.17 (P less than 0.001), respectively. These increments were due to increased non-renal clearances. The immunosuppressive activity as a function of time in plasma determined as the percent inhibition of the mixed lymphocyte reaction decreased by one third after phenytoin dosing, while the EC50 values of unbound prednisolone were unaffected. Thus enzyme induction decreases both the unbound prednisolone concentration and the steroid efficacy.

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Liquid-chromatographic measurement of endogenous and exogenous glucocorticoids in plasma.

Cited by 100 publications

References 0 publications

Impaired liver function in stable renal allograft recipients

Impaired liver function in stable renal allograft recipients

Alterations in prednisolone disposition as a result of time of administration, gender and dose.

Phenytoin modulates the pharmacokinetics of prednisolone and the pharmacodynamics of prednisolone as assessed by the inhibition of the mixed lymphocyte reaction in humans

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