Prednisolone binding to albumin and transcortin in the presence of cortisol

Rocci, Mario L.; D'Ambrosio, R; Johnson, Noreen F.; Jusko, William J.

doi:10.1016/0006-2952(82)90172-1

Cited by 48 publications

(41 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The other steroids do not bind to transcortin as do cortisol and prednisolone. 45 Another feature of this model, the dual cosine function, permitted asymmetric input rates of cortisol, allowing us to capture the nonmidpoint nadir of cortisol as well as the abrupt increase in cortisol concentrations seen between 18 and 20 hours.…”

Section: Discussionmentioning

confidence: 99%

“…The other steroids do not bind to transcortin as do cortisol and prednisolone. 45 Another feature of this model, the dual cosine function, permitted The lymphocyte pharmacodynamic model used in this study also differed from our previous studies. 2,42,43 In this study, a model that is capable of encompassing a substantial rebound component, as demonstrated by the return of T-helper and T-suppressor lymphocytes beyond corresponding baseline cell counts, was needed.…”

mentioning

confidence: 93%

See 1 more Smart Citation

Prednisolone Pharmacokinetics and Pharmacodynamics in Relation to Sex and Race

Magee

Blum

Lates

et al. 2001

The Journal of Clinical Pharma

Self Cite

111

View full text Add to dashboard Cite

Prednisolone pharmacokinetics (PK) and pharmacodynamics (PD) were investigated in relation to sex and race in white males, black males, white females, and black females (n = 8/group) after a single oral dose (0.27 mg/kg) of prednisone. The study consisted of baseline and prednisone phases with 32-hour sampling in each phase. Women were studied during the luteal phase of their menstrual cycle. Total and free plasma prednisolone concentrations were assayed by HPLC and ultrafiltration, and pharmacokinetic data were analyzed by compartmental fitting using WinNonlin. Plasma cortisol concentrations were assayed by HPLC; T-helper, T-suppressor lymphocyte, and neutrophil cell counts were determined by FACS and hemocytometry, and these pharmacodynamic data were evaluated by basic and extended indirect response models using ADAPT II. Total body weight-normalized free prednisolone oral clearance and apparent volume of distribution were higher in men compared with women, regardless of race (by22%in whites and40%in blacks for oral clearance, p < 0.01; by32%in whites and38% in blacks for apparent volume of distribution, p < 0.01). The 50% inhibitory concentration (IC 50 ) values for T-suppressor cell-trafficking inhibition were higher in whites than in blacks, regardless of sex (by 125% in men and 208% in women, p < 0.01). The IC 50 or SC 50 values for effects of prednisolone on cortisol secretion and T-helper lymphocyte or neutrophil trafficking were not statistically different between men and women, blacks and whites. The findings of this study suggest that there are some prednisolone PK/PD differences related to sex and race. However, these differences do not suggest the need for dosage adjustments, and additional experiments with repeat dosing are needed to fully evaluate the clinical implication of these findings.The role of sex as a factor in the pharmacokinetics and the pharmacodynamics (PK/PD) of drugs has become well appreciated. 1 Women often exhibit modestly more rapid clearances of drugs metabolized by the CYP3A4 pathway (e.g., methylprednisolone 2 ). They may also show alterations in the disposition of drugs in relation to the phase of the menstrual cycle (e.g., theophylline 3 ), pregnancy (e.g., caffeine 4 ), or after menopause (e.g., verapamil 5 ). Women receiving oral contraceptives are likely to show more rapid clearances of conjugated NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript drugs (e.g., oxazepam) but have reduced clearances of many oxidized compounds (e.g., prednisolone 6 ). Interpretation of data is sometimes complicated by the need to assess whether pharmacokinetic parameters are properly normalized for body weight differences and if the phase of the menstrual cycle was monitored.The assessment of pharmacodynamic differences between men and women requires control of pharmacokinetic factors and use of appropriate methodology to relate responses to plasma or biophase drug concentrations. There are some notable examples of marked sex differences in drug efficacy. As...

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 93%

Prednisolone Pharmacokinetics and Pharmacodynamics in Relation to Sex and Race

Magee

Blum

Lates

et al. 2001

The Journal of Clinical Pharma

Self Cite

111

View full text Add to dashboard Cite

show abstract

“…In vitro studies of prednisolone-cortisol binding interactions have demonstrated that these two compounds can mutually displace each other from transcortin but prednisolone has a 2.5-fold higher affinity than cortisol for this protein (Rocci et al, 1982 …”

Section: Discussionmentioning

confidence: 99%

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

Meffin¹,

Brooks²,

Sallustio³

1984

Brit J Clinical Pharma

View full text Add to dashboard Cite

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.

show abstract

“…solone-cortisol binding interaction (Rocci et al, 1982) and illustrate one of its in vivo consequences. The differences in free fraction also illustrate the artefacts that can be introduced into the estimation of parameters of free prednisolone disposition if samples used for protein binding determinations are not those taken during the disposition of the drug.…”

Section: Effects Of Cortisot On Prednisotone Ctearancementioning

confidence: 99%

“…At total prednisolone concentrations > 200400 ng/ml, binding to albumin is the major determinant of prednisolone free fraction. The binding affinity of prednisolone for albumin is 300 times that of cortisol (Rocci et al, 1982). Therefore immediately following high prednisolone doses administered at 08.00 h there is no effect of cortisol on prednisolone free fraction as total plasma prednisolone concentrations are greater than 500 ng/ml and by the time they have fallen to < 400 ng/ml, plasma cortisol concentrations are low (Figure 7).…”

Section: Effects Of Cortisot On Prednisotone Ctearancementioning

confidence: 99%

Alterations in prednisolone disposition as a result of oral contraceptive use and dose.

Meffin¹,

Wing²,

Sallustio³

et al. 1984

Brit J Clinical Pharma

View full text Add to dashboard Cite

1 The disposition of total and free prednisolone has been studied in eight female subjects who used combined oestrogen-progestogen oral contraceptives and in eight female subjects who did not, each of whom received separate intravenous doses of 0.1 mg/kg (low) and 1.0 mg/kg (high) of prednisolone. 2 Mean free prednisolone clearance was reduced -30% in oral contraceptive users compared to control subjects (P < 0.001), the difference being greater for the low dose (39%) than for the high dose (24%). Pre-dose plasma cortisol concentrations were elevated two-fold (P < 0.001) in oral contraceptive users compared to control subjects. These effects are consistent with a mechanism in which the competitive inhibition of free prednisolone clearance by cortisol contributes to the reduction of free prednisolone clearance by oral contraceptive use. 3 Mean total prednisolone clearance and steady state distribution volume showed an approximate two-fold dose dependent increase consistent with a similar increase in plasma prednisolone free fraction (P < 0.001). Free prednisolone clearance showed an 18% dose dependent decrease (P < 0.001) but free steady-state distribution volume did not change with dose. 4 At plasma prednisolone concentrations < 400 ng/ml, prednisolone free fractions at any prednisolone concentration were greater after the low, than after the high dose. This effect is consistent with the displacement of prednisolone by cortisol from transcortin but not from albumin.

show abstract

Prednisolone binding to albumin and transcortin in the presence of cortisol

Cited by 48 publications

References 8 publications

Prednisolone Pharmacokinetics and Pharmacodynamics in Relation to Sex and Race

Prednisolone Pharmacokinetics and Pharmacodynamics in Relation to Sex and Race

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

Alterations in prednisolone disposition as a result of oral contraceptive use and dose.

Contact Info

Product

Resources

About