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J D Henderson

Publications and source records attributed to J D Henderson.

At least 55 records · Page 3Linked to original sources
PubMed1985

Pharmacokinetic calculator program for generation of initial parameter estimates from a three-compartment infusion model.

A polyexponential curve-stripping program, KIN, is described for use on the HP-41CV programmable calculator. The program may be used in the analysis of plasma-concentration-time curves for a three-compartment intravenous bolus or infusion model with linear elimination processes. The coefficients and hybrid rate constants of the exponential function are then used to compute pharmacokinetic parameters (volume of the central compartment, intercompartmental rate transfer constants), which may be used as initial estimates of model parameters in non-linear regression curve-fitting procedures.

Computers↗
PubMed1985

DATALIN--an interactive data entry program for use with NONLIN.

A package of FORTRAN programs for data entry into NONLIN (version II) is described which may be used in the analysis of plasma-concentration time curves after single or multiple doses for fourteen pharmacokinetic models described in terms of the model's microconstants (volume of compartments, rate constants). In all cases, infusion rates must be zero-order and absorption rates first-order. The program contains an edit subroutine allowing for changes in initial parameter estimates and their lower and upper limits, weighting factors, number of iterations in the NONLIN analysis, and plot option. Individual X and Y values may be changed and listed and X-Y data pairs may be inserted or deleted. Factors pertaining to each of the data entries in relation to NONLIN are discussed.

Animals↗
PubMed1984

Gas chromatographic analysis of cetiedil, a candidate antisickling agent, in human plasma with nitrogen-sensitive detection.

In this report a sensitive gas chromatographic assay for cetiedil, a candidate antisickling agent, in human plasma is described. After a triple extraction procedure, cetiedil was analyzed without derivatization with a nitrogen-phosphorus detector (with papaverine used as the internal standard.) Cetiedil was measured in plasma samples taken from human volunteers administered the drug intravenously.

Adult↗
PubMed1983

Clinical effects of intravenous cetiedil, a candidate anti-sickling agent.

As part of a Phase I clinical trial, the clinical effects resulting from both single and multiple dose infusions of cetiedil, a candidate anti-sickling agent, were evaluated. Multiple doses of up to 0.45 mg/kg every six hours for four days were safe and well-tolerated in adult male volunteers. Most adverse reactions to cetiedil are related to its anticholinergic properties (dryness of mouth, blurred vision, spacy feelings, disorientation) or vasodilatory effects (light-headedness, vertigo, cold extremities); these side-effects were dose-related with regard to incidence, severity and duration. Moderate to slight reductions in systolic and diastolic blood pressure and pulse rate were statistically significant but no dose-related. There were no significant changes in respiratory rate, ECG, biochemical or haematological parameters. Adverse reactions were transient and required neither medical intervention nor discontinuance of infusions.

Adult↗
PubMed1981

A nonmetabolized analogue of phenytoin.

Nine novel analogues of 5,5-diphenylhydantoin bearing a CF3 group(s) in the meta or para position of one or both rings were synthesized. Preliminary evaluation of all the analogues (performed by the ADD Program, NIH) indicated no significant anticonvulsant activity against electrical or chemical shock in mice at doses of less than or equal to 100 mg/kg. The analogue 5,5-bis[4-(trifluoromethyl)phenyl]hydantoin (1) was synthesized labeled with 14C in the 4 position of the hydantoin ring. Certain physicochemical properties (pKa, partition ratio, protein binding, etc.) and the LD50 of 1 in mice (40 mg/kg, ip; 100 mg/kg, po) were determined. The disposition of [14C]1 was determined in rodents. The compound was excreted unchanged in rat feces (94% in 18 days), urinary excretion less than 0.5%. The half-life of elimination of [14C]1 from plasma was 67-72 h (ip and iv) in rats and 115 h (ip) in mice. Studies of tissue distribution and biliary excretion of [14C]1 indicate low tissue/plasma ratios (due to high plasma binding, 97%) and low biliary excretion. The lack of metabolism of [14C]1 may possibly be explained by (1) the strong electron-withdrawing effects of CF3 substituents, (2) the preemption of the primary metabolic sites, (3) the accompanying steric hindrance, and (4) the apparent inability of the CF3 group to undergo the NIH shift.

Animals↗
PubMed1980

Antiarrhythmic activity of amitriptyline analogues in conscious dogs after myocardial infarction: cyproheptadinium methiodide.

The antiarrhythmic effects of amitriptyline (1), its secondary amine metabolite nortriptyline (2), as well as cyclobenzaprine (3) and cyproheptadine (4), tertiary amine analogues of 1, were studied in conscious dogs 24 h after myocardial infarction. Since the sedative side effect of 4 presents a potential problem for its clinical use, a quarternary derivative of 4, cyproheptadine methiodide (5), was prepared and its effects also studied in this model. Complete conversion to a normal sinus rhythm occurred in all animals studied after cumulative doses of 1700 micrograms/kg (6.17 mumol/kg) of 3, 1300 micrograms/kg (4.69 mumol/kg) of 1, 300 micrograms/kg (1.04 mumol/kg) of 4, and 25 micrograms/kg (0.058 mumol/kg) of 5. While 2 significantly decreased ventricular ectopic activity, it did not convert any of the animals studied to a sinus rhythm at doses up to 3000 micrograms/kg. Thus, the order of potency for conversion to a normal sinus rhythm appears to be 5 >> 4 > 1 > 3 >> 2. These data suggest that 5 is very potent in converting ventricular arrhythmias associated wtih myocardial infarction.

Amitriptyline↗
PubMed1980

Ocular toxicity in beagle dogs with an experimental fluoromethane-sulfonanilide sympathomimetic agent.

ocular lesions were detected in Beagle dogs receiving high doses of BA6650, an experimental fluoremethane-sulfonanilide sympathomimetic agent, during a preclinical safety evaluation study. The oral dose of BA6650 was increased during the 14-day study from 20 mg/kg twice daily (bid) for days 1-3 to 30 mg/kg bid for days 4-6 and finally to 40 mg/kg bid for days 7-14. Two males and two females received BA6650 while one male and one female were not dosed. Intraocular pressure in the untreated controls fluctuated during the study between 17 and 22 mmHg. Intraocular pressure decreased in 3 of 4 BA6650 treated dogs from an initial mean value of 17 to a final mean value of 8 mmHg. Ocular lesions consisting of conjunctival hyperemia, corneal opacities, epiphora, mydriasis followed by miosis, corneal herniation, hypopyon, ptosis, and anterior synechia developed in three of the animals.

Animals↗
PubMed1976

Fluorescein angiography of the normal and diseased ocular fundi of the laboratory dog.

A method was determined for fluorescein angiography of the ocular fundus of the laboratory Beagle, using a portable fluorescein fundus camera. A 10% solution of sodium fluorescein was injected by a syringe pump in the right cephalic vein of each dog. Acepromazine maleate (0.5 mg/kg, IV) with ketamine hydrochloride (10 mg/kg, IM) provided chemical restraint. Of the 10-, 25-, and 50-mg/kg dosages of fluorescein, 25 mg/kg permitted satisfactory fluorescence of the choroidal and retinal vasculature and the recirculation phase. High-speed color film permitted good quality photography of the tapetal and nontapetal retinal vessels. Reduced retinal blood vessel and pigment epithelium permeability was demonstrated by fluorescein angiography in dogs with chorioretinitis associated with systemic blastomycosis, retinitis associated with distemper, serous retinal detachment, and preretinal hemorrhage.

Animals↗
PubMed1973

Induction cardiac pacing: a new approach.

A new approach to induction cardiac pacing using a "skin tunnel" transformer has been developed and used in a patient. Initial results are encouraging. If the system proves reliable in the long term it may have important applications in the delivery of power to implanted artificial organs.

Abdomen↗
PubMed1973

Accelerated triglyceride secretion. A metabolic consequence of obesity.

A new animal model was developed to determine the effect of obesity upon endogenous triglyceride secretion. Desert sand rats (Psammomys obesus), rodents which become spontaneously obese and hyperinsulinemic when given ad lib. chow, were given intravenous Triton to allow in vivo measurement of triglyceride secretion rates (TGSR). In a group of 18 fasted animals of varying body weight and degrees of obesity, TGSR correlated significantly with body weight (r=0.68, P < 0.01) indicating that obesity was associated with accelerated endogenous release of triglyceride. In these same animals, basal plasma insulin levels correlated significantly with body weight (r=0.78, P < 0.001) and TGSR correlated significantly with mean plasma insulin levels (r=0.73, P < 0.001), suggesting that hyperinsulinemia may have been the mechanism through which obesity enhanced TGSR. No correlation was found between basal triglyceride level and either body weight, basal insulin, or TGSR which suggested that individual triglyceride removal rates among the animals may have been variable. To test this hypothesis, seven animals were studied prospectively before and after induction of obesity. There were significant increases (P < 0.02) in all parameters, i.e., weight, plasma insulin level, TGSR, and basal triglyceride level. Thus, when each animal was used as its own control, thereby minimizing the postulated factor of variable individual triglyceride removal, increments in basal triglyceride were shown to accompany the development of obesity, hyperinsulinemia, and accelerated triglyceride secretion. These data from studies in the sand rat offer in vivo evidence that obesity leads to accelerated triglyceride secretion, an effect which may be mediated by hyperinsulinemai, and which can be invoked as one possible mechanism to explain hypertriglyceridemia associated with obesity in man.

Animals↗