Biomedical subjects
L E Domino
Publications and source records attributed to L E Domino.
Diagnosis of depression in alcoholics.
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Relation of plasma morphine concentrations to severity of abrupt withdrawal in morphine-dependent monkeys.
Plasma morphine levels were measured during abrupt withdrawal in four chronically dependent female monkeys. Approximately 12 hr after withdrawal, the morphine plasma concentrations were about 8 to 10 ng/ml, at which time all of the animals showed mild to moderate symptoms of opiate withdrawal. Severity of withdrawal showed a negative correlation (r = -0.93, P less than .001) with the falling phase of plasma morphine. It may be concluded that, under the conditions of this experiment, significant morphine withdrawal symptoms arose despite measurable plasma concentrations of morphine and that the relationship between plasma concentrations and withdrawal may be quantified according to a linear pharmacokinetic model for a given chronic dose (3.0 mg/kg q 6 hr) of morphine.
Relationship between plasma concentrations of clonidine and mean arterial pressure during an accidental clonidine overdose.
The time course of toxicity in a 28 year old man following a 100 mg accidental overdose of clonidine hydrochloride is compared with the decline of plasma clonidine over 5 days. The concentration data were analyzed by nonlinear least squares regression, and fitted to a model which dissociated the blood pressure effects into pressor and depressor components. According to this analysis, there appeared to be two phases of toxicity over time--a hypertensive, and a hypotensive phase. The hypotensive and the hypertensive phases may result primarily through differential stimulation of central alpha 2-, alpha 1-, and vascular post-synaptic alpha 2-adrenoceptors as plasma concentrations fall.
Ketamine kinetics in unmedicated and diazepam-premedicated subjects.
Plasma ketamine concentrations after diazepam and placebo pretreatment were examined in a double-blind, randomized, cross-over study. Eight healthy male subjects received either diazepam or a 0.9% NaCl placebo before ketamine and received the alternate combination 5 to 24 days later. Ten minutes before ketamine dosing, diazepam, 0.3 mg/kg, or placebo in equal volume was injected intravenously at a rate not exceeding 5 mg/min. Ketamine, 2.2 mg/kg iv, was injected over 1 min. For the clinically relevant period for anesthesia (1 to 30 min), diazepam-ketamine treatment resulted in higher plasma levels at most time points, but diazepam pretreatment did not alter plasma levels of metabolite KI and pseudometabolite KII nor the 24-hr urinary excretion of ketamine, KI, and KII. Ketamine kinetics followed a three-term exponential decline under both treatment conditions. After placebo-ketamine dosing, plasma t 1/2s were as follows: distribution (pi t 1/2) = 24.1 sec, redistribution (alpha t 1/2) = 4.68 min, and elimination (beta t 1/2) = 2.17 hr. After diazepam-ketamine dosing, t 1/2s were: pi t 1/2 = 25.0 sec, alpha t 1/2 6.37 min, and beta t 1/2 = 2.32 hr.
Is there "reverse tolerance" to marijuana?
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Comparison of two and three compartment models of phencyclidine in man.
A pharmacokinetic analysis comparing a 2 and 3 compartment model was performed on the published data of Wall et al. (12) on the kinetics of phencyclidine (PCP). These investigators gave 100 micrograms (mean 1.3 micrograms/kg) of 3H-PCP i.v. to three human volunteers and followed the plasma disappearance of PCP over 72 hr. They suggested that PCP followed a 2 compartment model with a plasma half life of 7-16 hr. In the present analysis, additional pharmacokinetic estimations from the plasma data were made and a 3 compartment model developed. The results obtained suggest complex PCP kinetics involving an initial pi half life of 5.5 min, an alpha half life of 4.6 hr, and a beta half life of 22 hr. The volume of distribution was large, varying from 2.2 to 2.4 1/kg for each compartment, suggesting binding of PCP.
Plasma levels of ketamine and two of its metabolites in surgical patients using a gas chromatographic mass fragmentographic assay.
Ketamine and two of its metabolites were determined up to 24 hours by a sensitive and specific gas chromatographic mass fragmentographic (GCMF) assay in the plasma of seven premedicated surgical patients. Each patient received ketamine in a dose between 2.0 and 2.2 mg/kg given intravenously over a 30-second period. Plasma levels of ketamine varied from 9,000 to 25,800 ng/ml 1 minute after injection to approximately 1,000 ng/ml when the patients began to recover consciousness. Within the next 24 hours, the patients had a complex logarithmic decline after injection. The data suggest rather complex pharmacokinetics with multiple compartments. Ketamine metabolites I and II were also found in the plasma over comparable periods of time. Ketamine metabolite I levels ranged from a high of 245 to 668 ng/ml within 30 minutes after ketamine administration to as low as 15 ng/ml 24 hours later. Ketamine metabolite II levels were lower with a peak of 515 ng/ml in approximately 60 minutes to 13 to 27 ng/ml 24 hours later. Recovery from anesthesia was related to the first two phases of rapid redistribution of ketamine. The plasma levels of the two ketamine metabolites were first detectable approximately 5 minutes after ketamine injection. Their relatively low levels throughout ketamine anesthesia and postanesthesia do not correlate with recovery from anesthesia. CSTRIP and NONLIN analysis indicated that a three-exponential equation best approximated the data obtained. It is concluded that a three-compartment open model best approximates ketamine pharmacokinetics in these patients.
Composition of the aqueous phase of chromaffin granules.
Nuclear magnetic resonance spectroscopy has been used to determine the composition of the aqueous phase of bovine chromaffin granules. Relative concentrations of catecholamines (epinephrine plus norepinephrine), ATP and chromogranins have been measured from integrated intensities in the proton spectra using computer simulation techniques. Most or all of the catecholamines (97 +/- 8%) are present in the aqueous phase and contribute to the high resolution spectrum. The catecholamine:ATP molar ratio (4.41 +/- 0.45) determined by NMR is close to the value (4.45) derived from biochemical assay indicating that most or all of the ATP is present with catecholamine in the aqueous phase. Catecholamine:protein ratios show that approximately 45% of the soluble protein freed by lysis is not NMR visible. Intensity from this fraction does not appear under highly denaturing conditions (8 M urea) but reappears after hydrolysis. This behavior is similar to that of recently isolated soluble lipoprotein complexes. Variations in the NMR spectra associated with (1) different preparative procedures; (2) different suspension media, and (3) increasing osmolality are described. The fact that high concentrations of epinephrine and ATP (approximately 700 mM total) are dissolved in the aqueous phase implies that solution phase interactions at least partially ionic in nature are responsible for the low internal osmolality of chromaffin granules in vivo. Ordered phases containing a substantial fraction of the total catecholamine in an osmotically inactive form are not present.
Differential effects of d-amphetamine on brain acetylcholine in young, adult and geriatric rats.
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Toxicokinetics of 2,2',4,4',5,5'-hexabromobiphenyl in the rat.
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