Effects of tobacco smoking and oral contraceptive use on theophylline disposition.

The independent as well as interactive effects of chronic (greater than 6 months) oral contraceptive (OC) use and cigarette smoking on single-dose (4 mg/kg) theophylline disposition were assessed in 49 young, healthy women. Significant elevations (40%) in theophylline plasma clearance were found in women who smoked. OC use resulted in decreases in clearance of a similar magnitude (28%).

Procainamide disposition in obesity.

The pharmacokinetics of intravenous procainamide (PA) were studied in seven obese and seven normal subjects. Serum concentrations and urinary excretion rates of PA and its active metabolite, NAPA, were measured by high performance liquid chromatography. Pharmacokinetic parameters were related to ideal body weight (IBW) and total body weight (TBW).

LAGRAN program for area and moments in pharmacokinetic analysis.

A computer program is described for examination of areas (AUC) and moments of serum concentration vs time data using the Lagrange technique alone or in conjunction with linear or log-trapezoidal methods. The suitability of the Lagrange polynomial approximations to the experimental data during AUC computation is possible through output of interpolated values between consecutive data points. Ill-fitting AUC's between any data points can be replaced with values generated by either trapezoidal method.

Prednisolone disposition and protein binding in oral contraceptive users.

Combined estrogen-progestogen oral contraceptives (OC) have been shown to alter the metabolism of certain drugs, including corticosteroids, as well as affect circulating protein concentrations. To assess these effects with regard to prednisolone, the pharmacokinetics and protein binding of this steroid were evaluated in eight female OC users and compared with results from eight male and five female non-OC users. All volunteers received 40 mg prednisolone, iv, and steroid concentrations were measured by high pressure liquid chromatography.

Binding of prednisolone to alpha 1-acid glycoprotein.

The binding of prednisolone to alpha 1-acid glycoprotein (AGP) was determined in vitro by equilibrium dialysis. The effects of temperature, protein concentration, and drug concentration were evaluated. The binding ratio (bound/free) correlated well with protein concentration (r = 0.

Effect of inflammatory bowel disease on absorption and disposition of prednisolone.

The pharmacokinetics and bioavailability of prednisolone after doses of oral prednisone and intravenous prednisolone were determined in seven patients receiving corticosteroids for treatment of inflammatory bowel disease in active disease and remission. Prednisone absorption and conversion to the active form of prednisolone was complete in both disease phases. Pharmacokinetic parameters for total and free (unbound) prednisolone did not differ significantly between disease phases.

Drug and metabolite concentrations combined in predicting steady-state concentrations from test doses.

The first day test dose versus steady-state relationship for predicting drug doses was evaluated for the situation where metabolites are produced. An organ clearance model incorporated into a digital computer program simulated drug and metabolite disposition. When the terminal elimination rate for metabolite was similar to that of its precursor, the drug and metabolite concentrations could be summed for use in test dose predictions as the resulting accumulation ratios were similar.

Effect on nephrotic syndrome on absorption and disposition of prednisolone in children.

The pharmacokinetics and bioavailability of prednisolone and prednisone after doses of 60 mg/m2 oral prednisone and 50 mg/m2 intravenous prednisolone were determined in six children receiving corticosteroids for treatment of nephrotic syndrome during active disease and in remission. Pharmacokinetic parameters were compared with values previously obtained from asthmatic children who received similar intravenous doses. In nephrotic children the area under the curve of prednisolone (AUCPn) was higher (by 134 +/- 42%) after oral doses of prednisone when compared to the intravenous prednisolone doses.

Dose- and time-related effect of troleandomycin on methylprednisolone elimination.

Effects of varying doses of troleandomycin (TAO) on methylprednisolone disposition were examined in five steroid-dependent asthmatic patients. The characteristic reduction in methylprednisolone elimination in the presence of TAO after a 40 mg IV methylprednisolone was also present after methylprednisolone doses as low as 4 mg. In patients receiving continuous TAO on an every-other-day basis, inhibition of methylprednisolone elimination was impaired to a greater extent on the "day on" TAO than on the "day off" TAO Methylprednisolone elimination on the day off TAO was still slower than that before TAO, however, TAO on a multiple-dose schedule resulted in greater reduction of methylprednisolone elimination than after a single TAO dose.

Steroid-specific and anticonvulsant interaction aspects of troleandomycin-steroid therapy.

Troleandomycin (TAO) is a macrolide antibiotic that has an apparent "steroid-sparing" effect when used in the treatment of severe steroid-dependent asthmatic patients. Recent observations demonstrated the effect of TAO on inhibiting methylprednisolone elimination, possibly contributing to its beneficial effects. Prednisolone and methylprednisolone disposition were studied before and 1 wk after initiation of TAO therapy in three patients.

Determination of metoprolol and alpha-hydroxymetoprolol in plasma by high-performance liquid chromatography.

A sensitive, selective and reproducible high-performance liquid chromatographic assay for the simultaneous determination of metoprolol and alpha-hydroxymetoprolol in plasma was developed with (+/-)-ethyl-2-(4-(3-isopropyl-amino-2-hydroxy-propoxy)phenyl)-ethyl carbamate as the internal standard. Samples were acidified and subjected to an organic wash to remove interfering neutral and acidic components. Final extraction is made from the alkalinized aqueous phase with methylene chloride.

Active metabolites of imipramine and desipramine in man.

Active hydroxy metabolites of imipramine (IMI) and desipramine (DMI) have been quantified in plasma and cerebrospinal fluid (CSF) from patients at steady-state. In plasma of prepubescent boys and adults the concentration of unconjugated 2-hydroxyimipramine is only 15% to 25% that of IMI; 2-hydroxydesipramine (OH-DMI) concentration, however, is usually 50% that of DMI and in some cases OH-DMI is the predominant compound. In CSF from adult patients the ratio of concentrations of OH-DMI/DMI is higher than in plasma.

Dose-dependent pharmacokinetics of mezlocillin in relation to renal impairment.

The dose dependence of mezlocillin pharmacokinetics was examined in relation to renal function after intravenous doses of 1 and 5 g in 16 subjects with various degrees of renal impairment. Dose and time-average model-independent physiological parameters were calculated from plasma concentration and urinary excretion data. Lack of superimposition of plasma concentration profiles occurred between dosage levels with a twofold exaggeration of areas under the curve produced between doses of 1 and 5 g.

Prednisolone binding to albumin and transcortin in the presence of cortisol.

The protein binding of prednisolone was assessed in a 5% albumin solution and in pooled human serum, alone and in the presence of various amounts of cortisol. Significant displacement of prednisolone from transcortin binding sites occurred with little or no change in transcortin binding capacity or affinity constant for prednisolone, suggesting competitive inhibition of prednisolone binding by cortisol. Little or no displacement of prednisolone from the protein binding sites on albumin occurred though a decrease in the number of binding sites (four vs two), and an increase in the affinity constant for the albumin-prednisolone interaction (4.

Effect of age and sex on theophylline clearance in young subjects.

The joint effects of age and gender on theophylline plasma clearance (Clp) were assessed using an analysis of covariance technique. Data from several literature sources and from our laboratory were collated for this analysis with only non-smoking subjects aged 1.3 to 30.

Disposition of pulse dose methylprednisolone in adult and paediatric patients with the nephrotic syndrome.

The disposition of a large pulse-dose of methylprednisolone was examined in paediatric and adult patients with the nephrotic syndrome. Plasma concentrations and urinary excretion rates were measured by high performance liquid chromatography. Most of the dose was metabolized, as indicated by urinary recovery of less than 10 percent of the dose.

Effect of chronic oral contraceptive steroids on theophylline disposition.

The effect of chronic oral contraceptive (OC) usage on the disposition of theophylline was examined. Aminophylline solution (4 mg/kg) was given orally to 8 healthy female non-OC users and to 8 healthy women who were chronic (greater than 6 months) OC users. The OC user group had a significantly lower total plasma clearance of theophylline than women not using OC (35.

Sulfasalazine metabolite pharmacokinetics in pediatric patients with inflammatory bowel disease: effects of disease activity, acetylator phenotype, and age.

The pharmacokinetics and protein binding of sulfapyridine (SP) and its major metabolite, acetylsulfapyridine (ACSP) were examined in 17 prepubertal children and 4 postpubertal adolescents receiving sulfasalazine (SASP) for treatment of inflammatory bowel disease (IBD). Five patients were studied in both active disease and remission. Comparisons were made with a group of 24 outpatients (9-62 years) with IBD controlled on SASP and in remission.

Dose-dependent protein binding and disposition of prednisolone in rabbits.

An animal model was sought that would mimic humans with regard to the dose-dependent pharmacokinetics of prednisolone. Four rabbits were each given 0.5 and 10 mg iv of prednisolone, and timed blood samples were obtained.

Mezlocillin disposition in chronic hemodialysis patients.

The pharmacokinetics of a single 1-g intravenous dose of mezlocillin were examined in six functionally anephric patients undergoing hemodialysis. Hemodialysis clearance calculated by plasma extraction ratios across the dialyzer membrane and by dialysis fluid agree well, averaging 26 and 32 ml/min. Dialyzer extraction ratios averaged 0.

Pharmacokinetic disposition of guanabenz in the rhesus monkey.

The pharmacokinetics of guanabenz (E-2,6-dichlorobenzylidene aminoguanidine acetate, Wy-8678) in rhesus monkeys given 14C-labeled and unlabeled drug were investigated. The radioactive dose was well absorbed after intragastric (ig) administration of 1 mg of the labeled drug per kg, as indicated by tissue and urinary recovery of the label. Excretion into urine accounted for 57 +/- 3 (SE)% of the radioactive ig dose.

Blood collection technique: no effect on in vitro protein binding of prednisolone.

The effect of the blood collection vessel and systemic heparin administration on in vitro protein binding of prednisolone was examined in blood collected from human subjects. No differences in the fractional binding of prednisolone were found in plasma from plain glass culture tubes, heparinized culture tubes, and two types of red- and green-top commercial vacuum tubes. Thus, these blood collection techniques do not alter serum or plasma albumin and transcortin binding of prednisolone.