PubMed Health⌕ Search

Biomedical subjects

G Labrecque

Publications and source records attributed to G Labrecque.

At least 37 records · Page 2Linked to original sources
PubMed1987

Time-dependent variations in the organ extraction ratios of acetaminophen in rat.

The pharmacokinetics of a single 40 mg/kg dose of acetaminophen was investigated at 09h00 and 21h00 in Sprague-Dawley rats synchronized to a 12-h light-dark cycle. Acetaminophen was administered by the intraarterial, intravenous, intraperitoneal, and oral routes in order to determine the contribution of the gastrointestinal tract, liver, and lung to the oral extraction ratio of the drug. A mean oral extraction ratio of 0.46 was obtained at 21h00 as compared to 0.39 at 09h00. The mean extraction ratios of the gastrointestine, liver, and lung were 0.05, 0.41, and 0 at 09h00 and 0.18, 0.24, and 0.13 at 21h00, respectively. These results indicate that the extrahepatic metabolism of acetaminophen is important at 21h00, but is barely detectable at 09h00, whereas the hepatic extraction ratio is higher at 09h00 than at 21h00. Thus, there are temporal variations in the disposition of acetaminophen in the rat.

Acetaminophen↗
PubMed1987

Chronopharmacology and chronotherapeutics: definitions and concepts.

Most knowledge of medications has been derived from single- and multiple-dose investigations in which pharmacokinetic and pharmacodynamic phenomena have been evaluated following one, usually, daytime drug administration. Chronopharmacologic studies involving the evaluation of such phenomena after each of several different clock-hour treatments during the day- and nighttime reveal that biological rhythmic processes, such as those of 24 hr, can profoundly affect the kinetics and effects of various medications. Several new concepts have arisen based on findings from chronopharmacologic investigations, such as chronokinetics, chronesthesy and chronergy. These are defined and discussed herein using illustrative examples. A major goal of chronopharmacologic research is to devise chronotherapeutic interventions. Chronotherapeutics is the optimization of drug effects and/or minimization of toxicity by timing medications with regard to biological rhythms. Chronotherapeutics takes into account predictable administration-time-dependent variation in the pharmacokinetics of drugs as well as the susceptibility of target tissues due to temporal organization of physiochemical processes and functions of the body as circadian and other rhythms. The unequally divided and once-daily theophylline treatment schedules for the clinical management of nocturnal asthma, which are discussed in this issue, represent steps toward a chronotherapy.

Animals↗
PubMed1987

[Basic mechanisms of chronopharmacology].

Many animal and human studies have demonstrated time-dependent changes in the effects and kinetics of drugs that can be explained in part by parallel changes in their absorption, metabolism and excretion. Although food influences drug absorption, its presence in the stomach does not explain the circadian rhythms in the absorption of xenobiotics. Circadian rhythms in blood flow, biliary secretion and the physico-chemical properties of drugs seem to be very important factors involved in the circadian rhythms of drug absorption. Time-dependent changes have been reported in the activity of hepatic enzyme involved in drug metabolism and they can explain the circadian rhythms in the effect of hexobarbital and in the kinetics of acetaminophen. However, circadian changes in blood flow, biliary secretion and in the binding to plasma proteins must be investigated thoroughly because they could explain many circadian rhythms in drug metabolism. The role of hepatic extraction ratio must also be looked at carefully. Finally, circadian changes in urinary pH, glomerular filtration and in other mechanisms of drug elimination by the kidneys can account for the circadian rhythms in the elimination of drugs such as the salicylates and furosemide. Future research on the molecular mechanisms of the circadian variations in the effects and kinetics of drugs must be carried out to give health professionals a better understanding of the phenomenon. Concepts and findings from investigative chronopharmacology are becoming now indispensable to solve problems of drug optimization.

Activity Cycles↗
PubMed1987

[The chronobiology of inflammation].

The inflammatory reaction is characterized by a multifrequency time structure with prominent circadian, ultradian and infradian rhythms in cell proliferation and cell function. The circulating blood cells show highly reproducible circadian rhythms in human and in animals. Daily fluctuations of concentrations of haematologic chemical and endocrinological parameters are described. Circannual variations of several hematologic parameters are presented. Chronobiological studies of plasma exudation in carrageenan paw oedema show a circadian and a circannual rhythm. Daily and annual changes in migration of polymorphonuclear leucocyte produced by BCG are studied in mice. Differences in response are observed in adrenalectomized and castrated animals. The susceptibility of cells and tissues at different stages of their circadian or circannual rhythms lead to the development of a chronotherapy of inflammation.

Animals↗
PubMed1986

Pharmacokinetics of a sustained-release product of indomethacin in the elderly.

The pharmacokinetics of indomethacin (Indo) was studied in 10 healthy elderly male volunteers (age 67-81 years) following the oral administration of a single 75-mg dose of a sustained release form of Indo. The total and free plasma and erythrocyte concentrations of Indo were determined by a specific high-pressure liquid chromatographic method. A maximum concentration (Cmax) of 4.28 +/- (SE) 0.43 micrograms/ml was reached after 1.85 +/- 0.22 h. The area under the plasma concentration versus time curve (AUC) was 22.83 +/- 2.70 micrograms ml-1 h and the plasma elimination half-life was 4.34 +/- 0.64 h. The maximum concentration of Indo in the red blood cells was 0.123 +/- 0.013 microgram/ml and was obtained at 1.95 +/- 0.14 h after drug administration. The erythrocyte concentrations of Indo represented 2.4% of the total plasma levels of Indo whereas only 1.3% of the drug was unbound to plasma proteins. The Cmax and AUC values determined in the elderly were approximately double the values reported in young adults for the same dose.

Administration, Oral↗
PubMed1986

Influence of BCG administration time on the in-vivo migration of leukocytes.

The temporal variation in the migration of polymorphonuclear leukocytes (PMN) induced by live BCG was studied in the mouse. Ten microliter of a 5 X 10(6) live BCG/ml suspension or sterile saline were placed on a cell trap immediately before its subcutaneous implantation at different clock times: 0100, 0500, 0900, 1300, 1700 and 2100 in animals synchronized with L(0700-1900): D(1900-0700). Eight hours later, the cell trap was removed, prepared for histological identification and counted. PMN counts in the cell trap were maximal 480 min after implantation. Non-specific migration was thought to occur and the peak value of leukocytes of 22.8 +/- 6.1 cells/10,000 micron 2 was obtained when the saline cell-trap was implanted at 0500. In the BCG-treated mice, a circadian rhythm was observed in the migration of leukocytes. The acrophase was at 1700. The results support the hypothesis that the circadian stage of antigen encounter influences the magnitude of the immune response.

Animals↗
PubMed1985

Monthly changes in the effect of BCG on the migration of polymorphonuclear leucocytes.

Monthly changes in the migration of polymorphonuclear leucocytes (PMN) produced by subcutaneous implantation of BCG-impregnated rayone-made disks was examined over a period of 15 months. In experiments carried out at 90h00, the highest PMN count of 40.2 +/- 8.4 PMN/10,000 micrometers2 10,000 micrometers2 was obtained in April. Mechanisms that could explain the circannual variation are suggested.

Animals↗
PubMed1984

Chronobiological study of plasma exudation in carrageenan-paw oedema in the rat.

The time-courses of exudation of protein-bound Evans' blue and of the formation of oedema following the injection of carrageenan (2 mg) or normal saline in the rat hind paw at 10.00 hours and 21.00 hours were studied. During the first 90 min after the carrageenan injection, the tissue content of the dye and the oedema formed were much greater when the inflammatory agent was administered at 21.00 hours than at 10.00 hours. A second study carried out at every 3 hours of the 24 hour span showed the presence of a circadian rhythm in the exudation of protein in the paw and in the formation of oedema. The paw volume and content of the dye were found to be highest between 19.00 hours and 01.00 hours whereas the minimal values were obtained at 16.00 hours. There is a correlation between the exudation of plasma proteins and the formation of oedema.

Animals↗
PubMed1984

Chronobiological studies on the hypotensive effect of prostaglandin E2 and arachidonic acid in the rat.

The present study was designed to determine whether biological rhythm variations could be detected in the hypotensive action of prostaglandin E2 (PGE2) and arachidonic acid (AA) in normal rats. Doses of 1.0 microgram kg-1 of PGE2 or 0.5 mg kg-1 of AA were administered to pentobarbital-anesthetized rats at 6 times of the day. Maximal reduction of systolic and diastolic blood pressures was obtained when PGE2 or AA were administered to rats between 0930 and 1200. The lowest falls in blood pressure were found when the same doses of the two substances were injected between 0300 and 0500. Mechanisms to explain these circadian variations are suggested.

Anesthesia↗
PubMed1984

Monthly variations in the clearance of antipyrine in the rat.

The variation in the pharmacokinetics of antipyrine was determined in synchronized rats over a period of 12 consecutive months. The mean values +/- SE (range) for the serum half-life, apparent volume of distribution and total body clearance of antipyrine were: 2.5 +/- 0.6 (1.6-4.9) h, 868.7 +/- 203.9 (590-1275) ml/kg and 269.2 +/- 14.7 (165-516) ml/h/kg respectively. The magnitude of the variation was three fold for the serum half-life and body clearance and two fold for the apparent volume of distribution. A new gas-liquid chromatographic assay for antipyrine is also described.

Animals↗
PubMed1983

Chronopharmacological studies of phenylbutazone in the rat.

Temporal variations in the anti-inflammatory action and in the ulcerogenic and lethal effects of phenylbutazone were studied in rats. The results indicate that small doses of the drug produced a larger reduction of paw edema in the morning than in the evening. At 0900, doses of 10, 30, and 100 mg/kg of phenylbutazone reduced the carrageenan-induced paw edema by 23, 44, and 66%, respectively. At 2000, the same doses of the drug decreased the paw edema by 9, 22, and 62%, respectively. No circadian variation was observed in the ulcerogenic effect of phenylbutazone. The mean lethal dose (LD50) of the drug was larger in the morning than in the evening and the values obtained were 710 +/- 24 (SE) mg/kg at 0900 in comparison to 525 +/- 38 (SE) mg/kg at 2000.

Animals↗
PubMed1982

Ketamine is the anesthetic of choice in studies on neocortical acetylcholine release.

The neocortical release of acetylcholine (ACh) and the effect of morphine on the release of the cholinergic transmitter were studied in ketamine-anesthetized and in midpontine pretrigeminal transected rats. The results show that control values for ACh release as well as the effect of morphine on neocortical ACh output were similar in both groups of rats. However, as ketamine produced some convulsive episodes in a few rats, continuous ECoG recording is recommended to avoid erroneous interpretation of the effects of drugs on the release of ACh.

Acetylcholine↗
PubMed1982

Circannual variations in carrageenan-induced paw edema and in the anti-inflammatory effect of phenylbutazone in the rat.

Circannual variation in the edema produced by intraplantar injection of carrageenan (carr) was examined over a period of 31 months. The anti-inflammatory effect of a dose of 30 mg/kg of phenylbutazone (PHZ) was also determined over a period of 1 year. Carr-induced edema was significantly larger in spring while it was smaller in winter. PHZ induced a pronounced reduction of paw edema throughout the year except in spring when the anti-inflammatory effect of the drug could not be detected. Mechanisms responsible for these circannual variations are discussed.

Animals↗
PubMed1982

Temporal variations in the effect of morphine and nalorphine on total brain acetylcholine content in the rat.

The effect of increasing doses of morphine and nalorphine on total rat brain acetylcholine (ACh) content was determined 30 min after the administration of the drugs at 07h30 and 19h30. The results indicate that the effects of morphine and nalorphine on brain ACh levels varied depending upon the time of administration. For instance, 10 mg/kg of morphine did not significantly change total brain ACh when injected in the morning whereas a 45% increase in ACh level was observed after administration of the same dose at night. Depending on the time of administration, nalorphine increased or decreased ACh content of rat brain. The results are discussed and related to the circadian rhythms that were demonstrated in brain levels of ACh, in opioid receptors and in the secretion of opioid peptides.

Acetylcholine↗
PubMed1980

Temporal variations in the elimination of antipyrine in normal and adrenalectomized rats.

An oral dose of antipyrine was administered at 08:00 and 20:00 hours to groups of sham operated and adrenalectomized rats standardized in an alternating 12-hour-light-dark cycle for 7 days prior the experiments. Temporal variations in the rate of elimination of antipyrine were obtained in both groups. Adrenalectomy decreased the serum elimination of antipyrine but had no effect on the temporal variations.

Adrenalectomy↗