scholarly journals Kinetic studies and production rate of melatonin in pony mares

1995 ◽  
Vol 268 (5) ◽  
pp. R1236-R1241
Author(s):  
D. Guillaume ◽  
N. Rio ◽  
P. L. Toutain
Keyword(s):  
Production Rate ◽  
Kinetic Studies ◽  
Volume Of Distribution ◽  
Systemic Availability ◽  
Intragastric Administration ◽  
Reproductive Pattern ◽  
Melatonin Concentration ◽  
Plasma Melatonin ◽  
Dose Levels ◽  
Melatonin Production

The aims of the present study were to determine basic kinetic parameters and the nycthemeral production rate of melatonin in the horse. Seven pony mares were used for the kinetic studies. Five other pony mares were used under long and short days for the production rate studies. Melatonin was administered by intravenous, oral, and intragastric routes at different dose levels. The plasma melatonin clearance was 1.02 +/- 0.31 l.kg-1.h-1, and the volume of distribution was 0.89 +/- 0.53 l/kg for the 0.4 microgram/kg melatonin dose. The systemic availability after oral and intragastric administration was consistently low (< or = 10%). The hourly melatonin production rates during short (36 +/- 33.6 ng.kg-1.h-1) and long nights (42 +/- 24.0 ng.kg-1.h-1) were not significantly different. It is concluded that the oral dose of exogenous melatonin required to control reproductive pattern in horses would need to be 10 times higher than the nocturnal melatonin production (0.5 microgram/kg) to obtain a physiological plasma melatonin concentration.

Genetic variability in melatonin concentrations in ewes originates in its synthesis, not in its catabolism

1998 ◽  
Vol 274 (6) ◽  
pp. E1086-E1090 ◽  
Author(s):  
Luis A. Zarazaga ◽  
Benoît Malpaux ◽  
Daniel Guillaume ◽  
Loys Bodin ◽  
Philippe Chemineau
Keyword(s):  
Pineal Gland ◽  
Genetic Difference ◽  
Volume Of Distribution ◽  
Breeding Value ◽  
Dark Phase ◽  
Melatonin Concentration ◽  
Blood Samples ◽  
Plasma Melatonin ◽  
Mean Residence Times ◽  
Melatonin Production

We investigated whether the genetic difference in plasma melatonin concentration in ewes was due to differences in the synthesis pathway from the pineal gland or in the catabolism of the hormone. Two groups of ewes [9 low (L) and 10 high (H)] were selected according to the breeding value of their mean nighttime plasma melatonin concentrations estimated at winter and summer solstices. In response to an identical dose of melatonin administered intravenously at 9:00 AM, no differences between groups were observed for any of the kinetic parameters: clearance rate, steady-state volume of distribution, terminal half-lives, and mean residence times. In the second experiment, two series of frequent blood samples were performed, one in the middle of the dark phase with samples taken every 5 min, and the other over 24 h with hourly samples. Highly significant differences between groups in nocturnal melatonin production rate were observed (L: 25.7 ± 2.8 vs. H: 63.1 ± 8.9 μg ⋅ kg−1⋅ h−1, P < 0.01). Thus the genetic differences in plasma melatonin concentrations in ewes originate in the synthesis pathway of the melatonin from the pineal gland rather than from differences in the catabolism of the hormone.

scholarly journals Effects of Duodenal 5-Hydroxytryptophan Perfusion on Melatonin Synthesis in GI Tract of Sheep

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5275
Author(s):  
Jun Pan ◽  
Fengming Li ◽  
Caidie Wang ◽  
Xiaobin Li ◽  
Shiqi Zhang ◽  
...  
Keyword(s):  
Portal Vein ◽  
Blood Circulation ◽  
Control Group ◽  
Melatonin Level ◽  
Gi Tract ◽  
Major Site ◽  
Melatonin Concentration ◽  
Plasma Melatonin ◽  
Melatonin Synthesis ◽  
Melatonin Production

The purpose of this study is to investigate the potential effects of 5-hydroxytryptophan (5-HTP) duodenal perfusion on melatonin (MT) synthesis in the gastrointestinal (GI) tract of sheep. 5-hydroxytryptophan is a precursor in the melatonin synthetic pathway. The results showed that this method significantly increased melatonin production in the mucosa of all segments in GI tract including duodenum, jejunum, ileum, cecum and colon. The highest melatonin level was identified in the colon and this indicates that the microbiota located in the colon may also participate in the melatonin production. In addition, portion of the melatonin generated by the GI tract can pass the liver metabolism and enters the circulation via portal vein. The current study provides further evidence to support that GI tract is the major site for melatonin synthesis and the GI melatonin also contributes to the circulatory melatonin level since plasma melatonin concentrations in 5-HTP treated groups were significantly higher than those in the control group. In conclusion, the results show that 10–50 mg of 5-HTP flowing into the duodenum within 6 h effectively improve the production of melatonin in the GI tract and melatonin concentration in sheep blood circulation during the day.

scholarly journals Kinetic studies and production rate of equine (e) FSH in ovariectomized pony mares. Application to the determination of a dosage regimen for eFSH in a superovulation treatment

2004 ◽  
Vol 182 (1) ◽  
pp. 43-54 ◽  
Author(s):  
C Briant ◽  
PL Toutain ◽  
M Ottogalli ◽  
T Magallon ◽  
D Guillaume
Keyword(s):  
Kinetic Parameters ◽  
Production Rate ◽  
Dosage Regimen ◽  
Latin Square ◽  
Kinetic Studies ◽  
Production Rates ◽  
Daily Production ◽  
Dosage Regimens ◽  
Dose Levels

The appropriate dosage regimen for equine FSH (eFSH) (dose, dosing interval) administration in a superovulation treatment in pony mares was determined by a kinetic approach using production rates and kinetic parameters of elimination of the hormone. Two dosage regimens were then tested in superovulation protocols. The eFSH production rates were determined by sampling four ovariectomized pony mares every 10 min for 8 h during the breeding season. Kinetic parameters were determined by administering four dose levels of a preparation of eFSH (4.4, 8.8, 17.6 and 35.2 micro g/kg) by the i.v. route to the same mares, in a randomized 4x4 Latin Square protocol. The overall mean plasma clearance was 0.256+/- 0.07 ml.kg(-1).min(-1), and was independent of the dose. The mean residence time ranged from 5.5 to 10.8 h and increased with the dose. The estimated FSH production rates were 8.6 to 15.3 micro g.kg(-1).day(-1) (i.e. 2.89 to 3.45 mg per day per mare). Two dosage regimens of eFSH were then tested in cyclic mares (ten treated mares in each trial): 3.45 mg per day (4.4 micro g/kg three times a day by the i.v. route), which corresponds to the maximal daily production rate of the native hormone in ovariectomized mares, and 1.72 mg per day (2.2 micro g/kg three times a day), which corresponds to half of that production rate. The dosage regimen of 2.2 micro g/kg three times a day gave satisfactory results in terms of efficacy (numbers of ovulations and embryos) with minimal unwanted effects (luteinized or anovulatory follicles).

scholarly journals Pharmacokinetics and Safety of Intravenous Ceftolozane-Tazobactam in Healthy Adult Subjects following Single and Multiple Ascending Doses

2012 ◽  
Vol 56 (6) ◽  
pp. 3086-3091 ◽  
Author(s):  
Benjamin Miller ◽  
Ellie Hershberger ◽  
David Benziger ◽  
MyMy Trinh ◽  
Ian Friedland
Keyword(s):  
Single Dose ◽  
Adverse Events ◽  
Healthy Adult ◽  
Volume Of Distribution ◽  
Dose Administration ◽  
Mean Values ◽  
Multiple Doses ◽  
Dosing Regimens ◽  
Dose Levels ◽  
Dose Limiting Toxicity

ABSTRACTThe pharmacokinetics and safety of ceftolozane, a novel cephalosporin, and tazobactam, a β-lactamase inhibitor, alone and in combination as a 2:1 ratio in single doses of up to 2,000 and 1,000 mg of ceftolozane and tazobactam, respectively, and multiple doses of up to 3,000 and 1,500 mg of ceftolozane and tazobactam, respectively, per day were evaluated in healthy adult subjects. In part 1, groups of six subjects each received single ascending doses of ceftolozane, tazobactam, and ceftolozane-tazobactam in a within-cohort crossover design. In part 2, groups of 5 or 10 subjects each received multiple doses of ceftolozane, tazobactam, or ceftolozane-tazobactam for 10 days. After a single dose of ceftolozane alone, the ranges of mean values for half-life (2.48 to 2.64 h), the total clearance (4.35 to 6.01 liters/h), and the volume of distribution at steady state (11.0 to 14.1 liters) were consistent across dose levels and similar to those observed when ceftolozane was coadministered with tazobactam. Mean values after multiple doses for ceftolozane alone and ceftolozane-tazobactam were similar to those seen following a single dose. The pharmacokinetics of the dosing regimens evaluated were dose proportional and linear. Ceftolozane-tazobactam was well tolerated and systemic adverse events were uncommon. Mild infusion-related adverse events were the most commonly observed following multiple-dose administration. Adverse events were not dose related, and no dose-limiting toxicity was identified.

scholarly journals Suppression of Melatonin 2-Hydroxylase Increases Melatonin Production Leading to the Enhanced Abiotic Stress Tolerance against Cadmium, Senescence, Salt, and Tunicamycin in Rice Plants

Biomolecules ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 589 ◽  
Author(s):  
Choi ◽  
Back
Keyword(s):  
Stress Tolerance ◽  
Transgenic Rice ◽  
Abiotic Stress Tolerance ◽  
Mrna Level ◽  
Transcript Level ◽  
Melatonin Concentration ◽  
Rice Plants ◽  
Cadmium Treatment ◽  
Melatonin Production

Melatonin 2-hydroxylase (M2H) catalyzes the conversion of melatonin into 2hydroxymelatonin (2OHM), which is present in plants at a higher concentration than melatonin. Although M2H has been cloned, the in vivo function of its product is unknown. Here, we generated stable T2 homozygous transgenic rice plants in which expression of endogenous M2H was suppressed (RNAi lines). However, we failed to generate M2H overexpression transgenic rice due to failure of somatic embryogenesis. The M2H transcript level showed a diurnal rhythm with a peak at night concomitantly with the peak concentration of 2OHM. RNAi rice showed a reduced M2H mRNA level and 2OHM and melatonin concentrations. The unexpected decrease in the melatonin concentration was caused by redirection of melatonin into cyclic 3hydroxymelatonin via a detour catabolic pathway. Thus, the decrease in the melatonin concentration in M2H RNAi rice led to slowed seedling growth and delayed germination. By contrast, the transient increase in the melatonin concentration was of greater magnitude in the M2H RNAi than the wild-type rice upon cadmium treatment due to possible suppression of melatonin degradation. Due to its higher concentration of melatonin, the M2H RNAi rice displayed tolerance to senescence, salt, and tunicamycin stresses. Therefore, the increase in the melatonin concentration caused by suppression of melatonin degradation or by overexpression of melatonin biosynthetic genes enhances stress tolerance in rice.

scholarly journals Perioperative plasma melatonin concentration in postoperative critically ill patients: Its association with delirium

2013 ◽  
Vol 28 (3) ◽  
pp. 236-242 ◽  
Author(s):  
Shiho Yoshitaka ◽  
Moritoki Egi ◽  
Hiroshi Morimatsu ◽  
Tomoyuki Kanazawa ◽  
Yuichiro Toda ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Melatonin Concentration ◽  
Plasma Melatonin

Seasons induce changes in the daily rhythm of plasma melatonin in goats (Capra hircus)

2015 ◽  
Vol 65 (1) ◽  
pp. 13-20 ◽  
Author(s):  
Vincenzo Carcangiu ◽  
Claudia Giannetto ◽  
Sebastiano Luridiana ◽  
Francesco Fazio ◽  
Maria Consuelo Mura ◽  
...  
Keyword(s):  
Jugular Vein ◽  
Reproductive Physiology ◽  
Daily Rhythm ◽  
Capra Hircus ◽  
Winter Solstice ◽  
Vernal Equinox ◽  
Melatonin Concentration ◽  
Plasma Melatonin ◽  
Natural Pasture ◽  
Natural Photoperiod

To evaluate the influence of natural photoperiod on the daily rhythm of melatonin, we assessed melatonin plasma concentration at four different times of the year. Ten Sarda breed goats were led to the natural pasture during the day and were kept in a common stall during the night. Blood samples were collected by means of a cannula inserted into the jugular vein, every two hours for a 24-hour period during the vernal equinox, summer solstice, autumn equinox, and winter solstice. Our results showed the existence of clear seasonal variation in the daily rhythm of plasma melatonin in goats, with the highest MESOR value in winter followed by spring. Acrophase was always observed in the middle of the scotophase. Robustness of the rhythm was higher in the spring as compared to the winter. Our results showed a daily rhythm of plasma melatonin concentration strongly related to the seasons. These results could be useful to establish appropriately timed melatonin and/or photoperiod treatments for the management of reproductive physiology in goats.

A pharmacokinetic study of Genetaxyl (G) together with cyclosporin A (CsA) administered orally in cancer patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 12002-12002
Author(s):  
C. Liau ◽  
E. Lepper ◽  
H. Wang ◽  
M. Yang ◽  
T. Chiou ◽  
...  
Keyword(s):  
Equilibrium Dialysis ◽  
Volume Of Distribution ◽  
Mean Value ◽  
Phase Ii Trials ◽  
Patients With Cancer ◽  
The Mean ◽  
High Concentrations ◽  
Apparent Bioavailability ◽  
Dose Levels ◽  
Dose Dependent

12002 Background: Oral administration of paclitaxel given with CsA has shown promising activity in Phase II trials, but the apparent bioavailability is low and dose-dependent due to the presence of high concentrations of Cremophor EL (CrEL). We hypothesized that the use of a novel oral paclitaxel formulation containing only 20% CrEL (Genetaxyl [G]; Genovate Biotechnology Ltd., Taiwan), given with CsA is associated with an improved pharmacokinetic (PK) profile. Methods: Cohorts of 6 patients with cancer were treated with oral G at a dose of 60, 120, or 180 mg/m2 and 10 mg/kg of oral CsA in cycle 1. In cycle 2, patients received IV G (175 mg/m2, 3-h infusion). Three additional patients received generic IV paclitaxel (GIP). Serial blood samples were analyzed by LC/MS/MS and equilibrium dialysis, to determine total and unbound paclitaxel PK. Results: The mean (± SD) total paclitaxel AUCs were 1299±189, 1682±636, and 2204±1407 ng.h/mL at the 3 consecutive dose levels, suggesting nonlinear PK. However, based on unbound AUC, the oral bioavailability was dose-independent (P=.62), with a mean value of 37.2±18.6% (n=15). As expected, the total paclitaxel AUC following IV G (9024±4648 ng·h/mL) was lower than that for IV GIP (13,732±3983 ng·h/mL), as a result of increased clearance (39.6 vs 18.3 L/h) and a larger volume of distribution (768 vs 268 L). Interestingly, the unbound paclitaxel AUC was similar between the two IV formulations (P=.25), as the ratio of unbound/total paclitaxel for G was 2.5 times higher than that for GIP (12.5 vs 4.9%). Toxicity profiles were mild, with only 2 patients experiencing ≥ Gr 3 myelosuppression following oral G at 180 mg/m2. Conclusions: The mean bioavailability of paclitaxel following oral Genetaxyl with CsA was about 37%, which is higher than that observed previously with paclitaxel (range, 21–31%). Further clinical exploration of oral Genetaxyl in taxane-sensitive diseases is warranted. [Table: see text]

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