Search PubMed⌕ Search

Biomedical subjects

C M Davis

Publications and source records attributed to C M Davis.

At least 73 records · Page 4Linked to original sources
PubMed1988

Pharmacokinetic factors affecting antidepressant drug clearance and clinical effect: evaluation of doxepin and imipramine--new data and review.

The selection of a starting dose for an antidepressant, and subsequent clinical titration to an appropriate therapeutic dosage, should be based on pharmacokinetic and pharmacodynamic principles. In the past decade, therapeutic monitoring of antidepressant drugs and use of pharmacokinetic principles have been shown to be an improvement over the dose-response approach. Endogenous (e.g., genetic metabolic phenotype, hepatic blood flow, and protein binding) and exogenous factors (e.g., smoking, dietary habits, concurrent medications) are capable of influencing physiological and pharmacokinetic variables in patients, accounting for the marked interindividual differences in the clearance rates of cyclic antidepressants. Interpatient variability for steady-state concentrations in plasma (Cpss) greater than 20-fold are observed at a fixed dose of imipramine (r2 = 0.525, df = 346, t = 19.541, P less than 0.0001) or doxepin (r2 = 0.506, df = 128, t = 11.403, P less than 0.0001). Analysis of doxepin in plasma vs estimated in oral clearance for 61 patients demonstrates a significant decline in oral clearance as a function of Cpss. At doses approaching the upper range recommended for the treatment of depression, Cpss appear to approach, in at least a few individuals, the maximum metabolic capacity of the patient (Vmax), leading to greater-than-expected increases in concentrations for a given dosage increment. Significant alterations in oral clearance are observed when medications are administered concomitantly. A greater-than-threefold difference in mean oral doxepin clearance rates is observed between two groups of patients receiving additional medications that are either inducers or inhibitors (P less than 0.0001, df = 32, t = 6.687). Pharmacokinetic principles defining and explaining the determinants of oral clearance can provide the clinician with a greater insight into the reasons for therapeutic failure and toxicity.

Aged↗
PubMed1987

The effect of spondylosis on the outcome of chemonucleolysis.

In an attempt to understand the relation between the outcome of chemonucleolysis treatment of lumbar discs and the presence of spondylosis (degenerative process) of the lumbar spine, 40 cases of disc herniation with subsequent intradiscal chymopapain injection (chemonucleolysis) were reviewed. Thirty-eight patients had plain radiographs, 25 had myelography, 28 had computed tomography (CT), and 15 had both myelography and CT. A review of these examinations revealed that 24 patients had minimal or mild spondylosis (group 1) and 13 patients had moderate spondylosis (group 2). Only one patient had a severe spondylosis (group 3). Chemonucleolysis failed in 8/24 (33%) patients from the first group and 2/13 (15%) cases from the second group. Therefore, the presence or absence of even moderate spondylosis did not affect the treatment success rate. A review of the 11 failed cases revealed spinal canal stenosis in three cases and a large disc herniation in two (one case with a myelographic block). Another case had a sequestered disc fragment. In two further cases, the disc herniation was far lateral with complete occlusion of the lateral foramen; another case exhibited severe degenerative changes of facet joints. In two other cases, treatment failure could not be explained by any radiographic finding. Of three patients with large disc herniation, only one responded successfully to intradiscal injection of chymopapain. Chemonucleolysis, however, failed in the only patient in the third group who had severe spondylosis of the facet joint.

Adolescent↗
PubMed1987

Voluntary wheel running exercise and monoamine levels in brain, heart and adrenal glands of aging mice.

The goals of this study were to examine the effects of three months of voluntary wheel-running exercise on life span, whole body and brain, heart and adrenal weights and biogenic amine content (norepinephrine, dopamine, epinephrine and serotonin) in three age groups of male mice. The three groups consisted of mature (9 months), middle-aged (19 months), and old (27-29 months) mice. No significant differences in weight were found between control and exercise or age. The oldest mice had a survival rate of 69% for the exercise group and 43% for the age matched controls when the exercise phase was completed. Locomotor activity was significantly reduced for the old mice compared to the middle-age and mature mice. Only the mature (12 months of age at sacrifice) exercised mice showed a cardiac and adrenal hypertrophy (about 10%). There was a moderate increase in norepinephrine content in the ventral hypothalamus of the brain with exercise (significant at 12 months of age). Biogenic amine content in other regions of the brain (brain stem and forebrain minus hypothalamus) was not affected by age and/or exercise. There was a significant decrease in heart norepinephrine content with exercise in old mice (30-32 months). Adrenal gland norepinephrine content was significantly increased by exercise at 12 months of age and decreased at 22 months of age. Our results suggest that an increase in norepinephrine content in the hypothalamus might be a manifestation of an adaptation to the increased demands upon hypothalamic noradrenergic terminals imposed by prolonged exercise. It is also apparent that aging and exercise alters the amounts of sympathetic transmitter of the heart and adrenal glands. Such alteration may be beneficial to the aging brain by retaining norepinephrine stores that normally decline with age.

Adrenal Glands↗
PubMed1987

The relevance of antenatal cardiotocography.

In a prospective study of 3,083 patients having antenatal cardiotocography it was shown that ominous fetal heart rate traces were most likely to occur when the test was applied in specific 'at risk' situations rather than as a routine screening test, and when the need for monitoring was perceived relatively early in the pregnancy. The majority of ominous traces were not preceded by a normal trace.

Female↗
PubMed1986

Effects of smoking on haloperidol and reduced haloperidol plasma concentrations and haloperidol clearance.

Plasma concentrations of haloperidol and its reduced metabolite (reduced haloperidol) were investigated in cigarette smokers (N = 23) and nonsmokers (N = 27). Steady-state plasma concentrations were obtained 12 h post bedtime dose. Haloperidol and reduced haloperidol concentrations were determined by RIA. Reduced haloperidol was separated by selective succinylation and liquid chromatography. Patients were clinically assessed with the Clinical Global Impression Scale (CGIS). Smokers had significantly lower haloperidol and reduced haloperidol plasma concentrations than nonsmokers (P less than 0.01, P less than 0.05). Clearance of haloperidol was significantly greater in smokers compared to nonsmokers (P = 0.0052). CGIS assessments did not show significant differences between smokers and nonsmokers. Plasma concentrations should be carefully monitored when patients either start or stop smoking.

Adult↗
PubMed1986

Bioavailability of psychotropic drugs: historical perspective and pharmacokinetic overview.

The evolution of the federal government's role in the regulation and evaluation of generic psychotropic medications is described. To place many of the methodologic bioequivalence issues for antipsychotic agents into perspective, the pharmacokinetics of these drugs are reviewed. Appropriate methodologies for studying the pharmacokinetics and pharmacodynamics of psychotropic drugs are in early developmental stages. Many of the issues relating to bioequivalence of generic products will not be resolved until a better understanding of these factors is developed.

Biological Availability↗
PubMed1986

Ipsilateral femoral neck and shaft fractures. Report of two cases using an alternate technique.

A technique for ipsilateral femoral neck and shaft fracture using the sliding compression hip screw with plate combined with trochanteric antegrade Ender nailing of the femur was applied in two cases. Ender nails can be passed without difficulty past a compression hip screw and the bicortical plating screws. The hip and femur can be fixed internally through a single approach in a single position. Sliding compression hip screw devices can provide excellent preliminary stable femoral neck fixation. Blood supply to the femoral head is not disturbed while the femoral intramedullary fixation is performed. Antegrade Ender nailing avoids the common knee complications associated with other retrograde techniques. Decreased operative time, less blood loss, less technical difficulty, and early mobilization are important factors in the multiple-injured patient. Femoral intramedullary fixation may require open reduction, circlerage to ensure stability, and maintenance of alignment in case of significant comminution to allow early crutch ambulation. This mode of fixation may be advantageous for selected cases.

Adult↗
PubMed1985

Quantification of reduced haloperidol and haloperidol by radioimmunoassay.

A radioimmunoassay for reduced haloperidol and haloperidol has been developed by using a simple derivatization-separation step prior to assay with an antibody cospecific for both compounds. The detection limit of the assay is less than 25 pg and shows no cross reactivity to other metabolites. The intraassay coefficient of variation for reduced haloperidol and haloperidol were 9.0 and 8.2% respectively and the interassay coefficients of variation were 9.0 and 10.6% respectively at 5-10 ng/ml. As many as 30 patient samples can be analyzed for both compounds in a single day.

Chromatography, Liquid↗
PubMed1985

Effects of carbamazepine on plasma haloperidol levels.

Plasma haloperidol levels were monitored in three schizophrenic patients when carbamazepine was either added or discontinued. The percent decrease in plasma haloperidol levels due to concomitant carbamazepine therapy was between 59% and 61%. The effects of carbamazepine on plasma haloperidol levels were noted to occur in 2 to 3 weeks. Although no adverse effects occurred in the patients during therapy, careful monitoring of clinical symptoms and plasma haloperidol levels is recommended.

Carbamazepine↗
PubMed1984

Quantitative determination of chlorpromazine and thioridazine by high-performance thin layer chromatography.

An assay for quantitation of chlorpromazine and thioridazine in patient plasma is developed. The procedure utilizes high-performance thin layer chromatography for separation and in situ absorption densitometry for quantitation. Depending upon the HPTLC plate size, 30 to 60 samples may be processed in less than 6 hr, with an intra-assay coefficient of variation of less than 4%. The procedure can be used to measure as little as 10 ng/ml of drug in plasma, well below expected concentrations in patients receiving these medications. Investigations of extraction procedures, sample application procedures, chromatographic conditions, sample derivatization, and in situ absorption densitometry are described.

Chlorpromazine↗
PubMed1984

Future of depot neuroleptic therapy: pharmacokinetic and pharmacodynamic approaches.

The future of depot neuroleptic therapy is discussed in terms of pharmacokinetic and pharmacodynamic research opportunities. Analytic methods for neuroleptic assays, including chromatographic, radioreceptor, nuclear magnetic resonance, and radioimmunoassay techniques, are briefly reviewed. Elucidation of depot neuroleptic multicompartment kinetics utilizing nonlinear mixed-effects modeling and the usefulness of these data in interpreting plasma levels are discussed. The clinical significance of plasma monitoring of depot fluphenazine, including the development of dosage conversion guidelines, is presented. The relationships between haloperidol and its metabolite reduced haloperidol (RH) are discussed in terms of dosage form and response. Clinical advantages resulting from the availability of more depot neuroleptics are discussed.

Adult↗
PubMed1984

Haloperidol and reduced haloperidol plasma levels in selected schizophrenic patients.

The first measurements of haloperidol (HL) and its reduced metabolite hydroxyhaloperidol (RH) in plasma versus clinical response in five chronic schizophrenic patients are reported. HL and RH were measured by a radioimmunoassay with a low coefficient of variation. Patients were selected based on poor response or the need for high dosage and were rated with the Clinical Global Impression Scale. Daily HL dosage range was 0.5 to 1.5 mg/kg. HL plasma concentrations ranged from 14 to 98 ng/ml. RH plasma concentrations ranged from 10 to 319 ng/ml. Four patients did not respond to HL therapy; two of these improved dramatically when switched to fluphenazine. The four nonresponding patients had higher RH than HL concentrations. RH seems to be present in plasma in significant concentrations, and further investigation of the relationships of RH and HL plasma levels versus response is needed.

Adult↗
PubMed1983

Determination of fluphenazine in plasma by high-performance thin-layer chromatography.

Determination of fluphenazine in blood plasma by in situ fluorescent detection after separation by high-performance thin-layer chromatography is described. Enhancement of fluorescent emission of the drug is accomplished by exposure to UV light in the presence of paraffin oil which permits a limit of detectability of approximately 0.1 ng/ml in blood plasma. Thirty samples or more can be processed in a 7-h period with excellent precision (less than 3% relative standard deviation at 2.5 ng/ml). Investigation of extraction procedures, chromatographic conditions, photodevelopment, and fluorescent detection are described.

Chromatography, High Pressure Liquid↗
PubMed1982

Total deafness.

Explore the source record for details and available documents.

Adolescent↗