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Biomedical subjects

M C Rogge

Publications and source records attributed to M C Rogge.

27 records · Page 2Linked to original sources
PubMed1989

The theophylline-enoxacin interaction: II. Changes in the disposition of theophylline and its metabolites during intermittent administration of enoxacin.

The pharmacokinetics of theophylline and its three major metabolites, 3-methylxanthine, 1-methylurate, and 1,3-dimethylurate, were studied during intermittent administration of enoxacin. The addition of enoxacin (400 mg, twice daily) to a theophylline dosing regimen (150 mg, twice daily) resulted in an immediate fall in plasma theophylline metabolite concentrations. Mean steady-state theophylline concentration in plasma during the dosing interval increased from 3.17 to 8.23 micrograms/ml. The mean 12-hour recovery of total theophylline metabolite decrease from 76.3 to 38.6 mg. After the discontinuation of enoxacin, but not theophylline, the plasma theophylline metabolite levels immediately increased to near or above the concentrations observed before enoxacin coadministration. Concurrently, theophylline concentrations decreased to levels equivalent to those observed before enoxacin coadministration. In general, the changes in plasma theophylline concentrations observed after the addition of discontinuation of enoxacin were complete within 3 days.

Adult↗
PubMed1989

In vitro and in vivo activities of WIN 54954, a new broad-spectrum antipicornavirus drug.

WIN 54954 (5-[5-[2,6-dichloro-4-(4,5-dihydro-2-oxazolyl)phenoxy]pentyl]-3- methylisoxazole) is a new member of the class of broad-spectrum antipicornavirus compounds known to bind in a hydrophobic pocket within virion capsid protein VP1. In plaque reduction assays, WIN 54954 reduced plaque formation of 50 of 52 rhinovirus serotypes (MICs ranged from 0.007 to 2.2 micrograms/ml). A concentration of 0.28 microgram/ml was effective in inhibiting 80% of the 52 serotypes tested (EC80). WIN 54954 was also effective in inhibiting 15 commonly isolated enteroviruses, with an EC80 of 0.06 microgram/ml. Furthermore, WIN 54954 was effective in reducing the yield of two selected enteroviruses in cell culture by 90% at concentrations approximately equal to their MICs. The therapeutic efficacy of intragastrically administered WIN 54954 was assessed in suckling mice infected with coxsackievirus A-9 or echovirus type 9 (Barty) 2.5 days prior to initiation of therapy. Single daily doses of 2 and 100 mg/kg protected 50% of the mice from developing paralysis (PD50) following infection with coxsackievirus A-9 and echovirus-9, respectively. At the PD50 doses for these two viruses, levels of WIN 54954 in serum were maintained above the in vitro MICs for a significant portion of the dosing interval. The dose-dependent reduction in viral titers observed in coxsackievirus A-9-infected mice correlated well with the therapeutic dose response. The potency and spectrum of WIN 54954 make it a potentially useful compound for the treatment of human enterovirus and rhinovirus infections.

Animals↗
PubMed1988

The theophylline-enoxacin interaction: I. Effect of enoxacin dose size on theophylline disposition.

Theophylline interacts pharmacokinetically with a variety of other drugs. Recently enoxacin was found to change theophylline's disposition. In a four-subject, four-way crossover study enoxacin was administered every 12 hours at four levels (0, 25, 100, and 400 mg) for 14 doses. With the ninth dose of enoxacin, 200 mg theophylline was coadministered. Blood and urine samples were assayed by sensitive and specific assays for the parent drugs and their metabolites. Significant reduction in the formation of theophylline's three major metabolites occurred on coadministration of enoxacin. At the 400 mg dose level, enoxacin caused a threefold decrease in theophylline's plasma clearance, a fourfold decrease in the urinary recovery of 3-methylxanthine and 1,3-dimethylurate, and a threefold decrease in the recovery of 1-methylurate.

Adult↗
PubMed1985

Vancomycin disposition during continuous ambulatory peritoneal dialysis: a pharmacokinetic analysis of peritoneal drug transport.

Expressions are presented to describe the absorption and also clearance of drugs administered into the peritoneal cavity of patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Application of the expressions to vancomycin kinetics in five male CAPD patients showed that therapeutic levels of vancomycin can readily be achieved and maintained in the systemic circulation by administering the appropriate loading and maintenance doses. The intrinsic peritoneal clearance of vancomycin reported here is higher than the apparent clearances reported previously, averaging 300 to 500 ml/min under the conditions used in this study. The low apparent clearances previously reported are useful clinically although they do not represent the true efficiency of vancomycin removal by CAPD. The degree to which apparent clearance underestimates the true intrinsic clearance is exponentially related to the dwell time of dialysate in the peritoneum. Intraperitoneal administration is a practical alternative to other routes for CAPD patients needing antibiotic or other therapy.

Adult↗
PubMed1984

Bioavailability of hydrochlorothiazide from tablets and suspensions.

The bioavailability of hydrochlorothiazide was determined following single oral 25-, 50-, 100-, and 200-mg tablet and suspension doses in 12 healthy male volunteers. Plasma and urine levels of hydrochlorothiazide were determined by HPLC. Plasma levels of hydrochlorothiazide were satisfactorily described by a triexponential function. Mean peak plasma levels, Cmax (127-135, 270-280, and 437-490 ng/mL from the 25-, 50-, and 100-mg doses, respectively) were dose proportional, as were areas under plasma profiles, AUC0----36. Mean percentage recovery of unchanged hydrochlorothiazide in 48-h urine samples accounted for 50-59, 54-55, 60-63, and 54-57% of the 25-, 50-, 100-, and 200-mg doses, respectively. There were no significant differences among these values. Correlation coefficients between 48-h urinary recovery of hydrochlorothiazide and the plasma values (Cmax and AUC0----36) for the 25-, 50-, and 100-mg doses were 0.73 and 0.84. There were no differences in the net increases in electrolyte excretion among the treatments during the 0-12-h postdose period. The systematic availability of hydrochlorothiazide, unlike that of chlorothiazide, is dose proportional in the therapeutic range.

Adult↗
PubMed1984

Bioavailability of hydrocortisone from commercial 20-mg tablets.

The relative bioavailability of hydrocortisone was determined from four different 20-mg tablet formulations and one suspension in 15 healthy male volunteers; results were compared with in vitro dissolution rates. Plasma levels of hydrocortisone were determined by a liquid chromatography method developed in this laboratory. Dissolution of the tablet formulations, using the official USP test, varied from 7.8 to 93.8% in 30 min. Similar plasma profiles were obtained from all tablet products, and there were no differences among tablets in the cumulative percentage of drug absorbed. There were no clear trends in any pharmacokinetic parameter values among the tablet dosages, and the four products were considered bioequivalent. The suspension dosage yielded significantly higher plasma levels compared with some of the tablet formulations during the initial 30-min postdose, significantly higher cumulative absorption at 0.5 and 1.0 h compared with one tablet formulation, and significantly higher ka and Cmax, and shorter tmax values, compared with some of the tablets.

Adult↗
PubMedDate not supplied

A pharmacokinetic comparison of cephalexin and cefadroxil using HPLC assay procedures.

The pharmacokinetics of cephalexin and cefadroxil were compared following single 500 mg oral doses to 12 healthy male volunteers. Doses were administered after an overnight fast according to a crossover design. Plasma and urinary levels of both compounds were determined by HPLC procedures. Cephalexin was absorbed rapidly, achieving a mean peak plasma level of 17.5 micrograms ml-1 at 1 h, compared to 16 micrograms ml-1 at 1.8 h for cefadroxil. Elimination half-lives of cephalexin and cefadroxil were 0.7 and 1.1 h, respectively. The area under the cefadroxil plasma curve was significantly larger than that for cephalexin. However, after allowing for differences in elimination rate constants and assuming equal distribution volumes, plasma data indicated the compounds were equally well absorbed. Only 70 per cent of cefadroxil was recovered in urine compared to 87 per cent of cephalexin during the 12 h following drug administration. The therapeutic significance of the different pharmacokinetic characteristics of cephalexin and cefadroxil, if any, may be a function also of their pharmacologic activity and/or the sensitivity of the target organism.

Adult↗
PubMedDate not supplied

Single dose and steady-state pharmacokinetics of adinazolam after oral administration to man.

An aqueous solution containing 1 mg of adinazolam mesylate per ml was administered orally as a single dose (40 mg) and with loading doses followed by hourly doses such that final dose rates of 1, 2, and 3 mg h-1 were administered to steady-state. Four subjects exhibited linear steady-state kinetics, while the other four exhibited Michaelis-Menten kinetics, based on measurement by HPLC of both unchanged drug and the major N-demethyl metabolite. The drug is very rapidly absorbed and has an intrinsic clearance of total (bound + free) drug which averaged 2.14 l min-1 based on the steady-state data and 1.17 l min-1 based on the single dose data, but these means do not differ significantly. The apparent metabolite clearance, CLmc/fm (where fm = fraction of adinazolam converted to the N-demethyl metabolite), averaged 0.170 l min-1 based on steady-state data and 0.179 l min-1 based on single dose data and these means do not differ significantly. Pharmacokinetic parameters, such as these clearances, had large intersubject variations. Three types of bioavailabilities were estimated from the data.

Administration, Oral↗