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Biomedical subjects

J R Latts

Publications and source records attributed to J R Latts.

8 recordsLinked to original sources
PubMed1991

The absolute bioavailability and dose proportionality of intravenous and oral dosage regimens of recainam.

Recainam is a novel class I antiarrhythmic agent with electrophysiologic characteristics of all three subclasses. The authors evaluated the absolute bioavailability and dose proportionality of three oral doses and two 2-stage intravenous (IV) infusion doses. Single oral doses of 200, 400, and 800 mg and IV infusions consisting of 0.8 mg/kg/5 min + 1.2 mg/kg/hr (3.75 mg/kg) and 1.6 mg/kg/5 min + 1.2 mg/kg/hr for 4 hours and 55 minutes (7.50 mg/kg) were administered to 15 healthy men. Plasma and urine samples were collected during the 36-hour period after drug administration and analyzed for recainam concentrations by HPLC. No significant differences were found in any of the pharmacokinetic parameters between the two IV dosage regimens. The absolute bioavailability of orally administered recainam increased from 73% for the 200 mg dose to 81% and 84% for the 400 and 800 mg doses, respectively. Dose proportionality deviated from linearity by 13% for the 200 vs. 400 mg doses, and 10% for the 400 vs. 800 mg doses. The slight deviation from linearity was apparently caused by increased absorption at the higher oral doses. The slight disproportionality in the disposition of recainam is not expected to be clinically significant.

Administration, Oral↗
PubMed1986

Clinical pharmacokinetics and metabolism of bevantolol.

Bevantolol (the hydrochloride salt) has pharmacokinetic properties that are clinically advantageous. Bevantolol is well absorbed orally (greater than 70%); and the systemic bioavailability is 60%. Peak plasma concentrations are achieved 1 to 2 hours following an oral dose. Elimination is first-order with an average elimination half-life of 1.5 hours. Bevantolol exhibits linear pharmacokinetics within the therapeutic range (100 to 400 mg) with no change in half-life with chronic dosing. These properties result in predictable plasma levels and predictable drug response.

Adrenergic beta-Antagonists↗
PubMed1983

The aminoglycoside panel: a new approach to monitoring aminoglycoside therapy.

The aminoglycoside antibiotics gentamicin and tobramycin have been monitored traditionally by measuring peak and trough drug levels in serum. We found interpretation of these data to be hazardous, due to variations in the drug administration-specimen collection process and routine medical events and practices. We describe an aminoglycoside panel consisting of three serum levels drawn across one dosage interval. Gentamicin and tobramycin were measured by an enzyme immunoassay. 430 panels (1,290 samples) were evaluated by determining each panel's conformity to a classical monoexponential decay curve. Panels were then categorized by pattern of fit to this model. Sixty-two percent of the panels fell within acceptable limits of the model, while 13% displayed obvious errors. The percentage of acceptable panels on nursing units given an intensive educational program on the proper protocol for drug administration-specimen collection procedures was increased compared with the rest of the hospital. We propose the adoption of the aminoglycoside panel for the routine monitoring of these antibiotics as a means of gauging specimen and data quality.

Aminoglycosides↗
PubMed1980

Histocompatibility antigens and gold toxicity: a preliminary report.

To investigate the possibility that genetic factors are involved in the outcome of gold salt therapy for arthritis, histocompatibility antigens (HLA) were determined for 32 patients treated with gold salts. A comparison of patients who achieved remission following gold therapy with those who did not failed to demonstrate any difference in HLA antigens. Patients who had experienced adverse reactions during gold therapy were found to have an increased frequency of the HLA-B12 antigen. Gold toxicity occurred in 69.2 per cent (9/13) of patients with the B12 antigen, compared with 26.3 per cent (5/19) of patients without the antigen (P = 0.035).

Adult↗
PubMedDate not supplied

Bioavailability of propranolol hydrochloride tablet formulations: application of multiple dose crossover studies.

Two multiple dose crossover pharmacokinetic studies were carried out to determine the steady-state bioavailability of newly formulated generic propranolol HCl tablets relative to Inderal tablets. In Study I, 24 healthy volunteers were dosed with 4 x 10 mg test tablets, 1 x 40 mg test tablet, 4 x 10 mg Inderal tablets, and 40 mg of propranolol HCl in solution. In Study II, 24 healthy volunteers were dosed with 1 x 80 mg test tablet, 1 x 80 mg Inderal tablet, and 80 mg of propranolol HCl in solution. Both studies were of randomized design with each formulation administered every 8 h for 15 doses. Serial plasma samples were obtained for 8 h after morning doses on Days 4 and 5 of each treatment period and assayed for propranolol using a validated HPLC method. Mean plasma concentration-time data for test tablets and reference tablets were superimposable in both studies. Pharmacokinetic parameters from Days 4 and 5 were combined for statistical analysis since subjects were determined to have reached steady-state. Mean AUC, Cmax, tmax, and Cmin values were not statistically different between test tablets and Inderal tablets in either study. Based on these findings, the test tablets demonstrated the same rate and extent of propranolol absorption as did corresponding Inderal tablets. Therefore, the test tablets and Inderal tablets were determined to be bioequivalent.

Biological Availability↗
PubMedDate not supplied

Influence of food on the pharmacokinetics of quinapril and its active diacid metabolite, CI-928.

A randomized two-way crossover study was conducted in 12 healthy volunteers to assess the effect of food on the pharmacokinetics of quinapril (CI-906) and its active metabolite, CI-928, after quinapril dosing. Forty-milligram oral quinapril doses were administered in a fasted or a fed state with a one-week washout period between treatments. No significant treatment differences were observed in quinapril and CI-928 values for maximum plasma concentration, area under the plasma concentration-time curve, or percentage of dose excreted in the urine. Small but significant increases of less than 0.5 hour in quinapril and CI-928 tmax values were observed after consumption of food. The pharmacokinetic profiles of quinapril and CI-928 were not significantly altered by the administration of food.

Adult↗
PubMedDate not supplied

The in vivo measurement of expired 14CO2 derived from the N-demethylation of aminopyrine as a reflection of the in vitro hepatic cytochrome P-450 drug-metabolism activity in rats.

The kinetics of 14CO2 production in rats were investigated after oral, ip, or iv administration of 14C-aminopyrine (AP) at several dose levels, and after pretreatment with phenobarbital (PB) or partial hepatectomy to produce alterations in hepatic function. Several kinetic parameters were assessed with each route of administration and at each dose level (0.1, 10, and 50 mg/kg). The parameters found most useful were: time to reach peak, peak rate, 14CO2 production per min at 20 or 30 min expressed as percentage of total administered 14C (R20 or R30), and half-life of the decline in 14CO2 production after peak. It was found that the R30 value after oral administration or R20 after the ip administration of AP (10 mg/kg) reflected alterations in hepatic function without significant overlap of values. The use of the R20 or R30 parameters determined from a single collection was further assessed in control and in PB- and CoCl2-pretreated animals and found to be capable of distinguishing between these different groups of animals. In addition, the AP breath test (ABT) kinetics were not significantly affected by 3-methylcholanthrene pretreatment. In another set of experiments, R30 values determined in controls and in PB- and CoCl2-pretreated rats demonstrated excellent correlation to changes in hepatic microsomal AP and ethylmorphine N-demethylase and aniline hydroxylase activities and cytochrome P-450 content. similar correlations were obtained with R20 after the ip administration of 10 mg of AP per kg. These findings indicate that the ABT is capable of accurately assessing AP N-demethylase activity and other parameters of hepatic mono-oxygenase activity.

Administration, Oral↗