Effects of body weight, smoking status and sex on plasma concentrations of once-monthly paliperidone palmitate

2021 ◽  
Author(s):  
Georgios Schoretsanitis ◽  
Ekkehard Haen ◽  
Daria Piacentino ◽  
Andreas Conca ◽  
Katharina Endres ◽  
...  
Keyword(s):  
Body Weight ◽  
Smoking Status ◽  
Plasma Concentrations ◽  
Paliperidone Palmitate

scholarly journals P332 Population pharmacokinetics of ozanimod and active metabolite CC112273 in patients with ulcerative colitis

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S355-S357
Author(s):  
J Shen ◽  
D Tatosian ◽  
L Sid-Otmane ◽  
N Teuscher ◽  
L Chen ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Body Weight ◽  
Drug Exposure ◽  
Smoking Status ◽  
Plasma Concentrations ◽  
Hepatic Function ◽  
Population Pk ◽  
Apparent Clearance ◽  
Post Hoc ◽  
The Impact

Abstract Background Ozanimod is an oral small molecule sphingosine 1-phosphate receptor modulator approved for relapsing forms of multiple sclerosis (RMS) and under development for ulcerative colitis (UC) and Crohn’s disease (CD). Following multiple dosing of ozanimod in healthy subjects, ozanimod and two of the active metabolites CC112273 and CC1084037 represent approximately 6%, 73%, and 15% of circulating total active drug exposure, respectively. Two separate pharmacokinetic (PK) models were developed for the most prominent metabolite CC112273 and ozanimod. CC1084037 was not modeled due to the high correlation between CC112273 and CC1084037 plasma concentrations. Therefore, this analysis aims to characterise the PK of ozanimod and the major metabolite CC112273 in UC and RMS population. Methods Subjects from 11 studies (Phase 1 to Phase 3) in healthy volunteers, RMS, and UC patients were included in this population PK analysis. The analyses included a total of 18901 concentrations from 2890 subjects for CC112273 and 18834 PK concentrations from 2977 subjects for ozanimod. A 2-compartment model was used to describe the concentration-time profiles of both ozanimod and CC112273, separately. The influence of weight, age, sex, race, disease, or smoking status and hepatic function on the PK of ozanimod and CC112273 were explored. The impact of concomitant corticosteroids on CC112273 PK were evaluated post hoc. Results While the overall apparent clearance of ozanimod was 7% lower in RMS patients compared to UC, similar exposures were observed in both populations. The most influential covariate on ozanimod PK was body weight, with a modest 23% increase in apparent clearance for a 102-kg subject relative to a 70-kg subject (Figure 1). The apparent clearance of CC112273 was 16% greater in RMS patients compared to UC patients, resulting in a slightly higher exposure for UC patients. Increasing body weight had a modest reduction in clearance, while smoking had the largest influence on CC112273 PK of approximately 108% increased clearance (Figure 2). Post-hoc results showed no impact of concomitant prednisone or prednisolone on the PK of CC112273. Other factors, including age, race, sex, or hepatic impairment did not impact the PK of ozanimod or CC112273 PK. Conclusion The population PK model of CC112273 indicates that covariates with the largest effect on CC112273 PK parameters were body weight and smoking status. However, no covariate impacted clearance by more than 25%. The PK of ozanimod and CC112273 were not meaningfully impacted by age including in the elderly, body weight, race, sex, hepatic function, or concomitant prednisone or prednisolone. Overall, the PK of ozanimod and CC112273 were comparable in UC and RMS patients.

INFLUENCE OF METYRAPONE ON PLASMA CONCENTRATIONS OF TESTOSTERONE AND ANDROSTENEDIONE IN MAN

1971 ◽  
Vol 68 (3) ◽  
pp. 576-584 ◽  
Author(s):  
K. O. Nilsson ◽  
B. Hökfelt
Keyword(s):  
Body Weight ◽  
Male Patient ◽  
Gradual Increase ◽  
Plasma Concentrations ◽  
Plasma Testosterone ◽  
Testosterone Levels ◽  
Basal Plasma ◽  
Normal Males ◽  
A Minor ◽  
Secondary Hypogonadism

ABSTRACT Metyrapone was administered either orally, 750 mg every four h, in a total of six doses, or intravenously 30 mg per kg body weight as a four h infusion. In three males with normal endocrine functions, metyrapone given orally or intravenously induced a fall in plasma testosterone and an elevation of androstenedione within 2–8 h. When metyrapone was administered to a patient given dexamethasone to suppress endogenous ACTH production, the androstenedione levels did not alter whereas the testosterone levels showed a slight, transient decrease. In two normal females metyrapone administration was followed by a marked increase in plasma androstenedione whereas testosterone showed only a minor, gradual increase. In one male patient with Addison's disease the basal plasma testosterone was normal whereas the level of androstenedione was low. Following metyrapone intravenously, there was a slight suppression of plasma testosterone but no change in the androstenedione concentration. In one patient with primary hypogonadism, two with secondary hypogonadism and two with Klinefelter's syndrome the plasma testosterone was low under basal conditions and did not change following metyrapone. Basal plasma androstenedione was within the range for normal males and increased markedly following metyrapone in all the cases.

Effects of ageing and exogenous melatonin on pituitary responsiveness to GnRH in rats

Reproduction ◽  
2000 ◽  
pp. 151-156 ◽  
Author(s):  
E Diaz ◽  
D Pazo ◽  
AI Esquifino ◽  
B Diaz
Keyword(s):  
Body Weight ◽  
Reproductive System ◽  
Plasma Concentrations ◽  
Pituitary Hormones ◽  
Female Rats ◽  
Control Groups ◽  
Melatonin Treatment ◽  
Exogenous Melatonin ◽  
Reproductive Axis ◽  
Effect Of Age

The effect of age and melatonin on the activity of the neuroendocrine reproductive system was studied in young cyclic (3-5 months-old), and old acyclic (23-25 month-old) female rats. Pituitary responsiveness to a bolus of GnRH (50 ng per 100 g body weight) was assessed at both reproductive stages in control and melatonin-treated (150 micrograms melatonin per 100 g body weight each day for 1 month) groups. After this experiment, female rats were treated for another month to study the influence of ageing and melatonin on the reproductive axis. Plasma LH, FSH, prolactin, oestradiol and progesterone were measured. A positive LH response to GnRH was observed in both control groups (cyclic and acyclic). However, a response of greater magnitude was observed in old acyclic rats. Melatonin treatment reduced this increased response in acyclic rats and produced a pituitary responsiveness similar to that of young cyclic rats. FSH secretion was independent of GnRH administration in all groups, indicating desynchronization between LH and FSH secretion in response to GnRH in young animals and during senescence. No effect on prolactin was observed. Significantly higher LH (3009.11 +/- 1275.08 pg ml(-1); P < 0.05) and FSH concentrations (5879.28 +/- 1631.68 pg ml(-1); P < 0.01) were seen in acyclic control rats. After melatonin treatment, LH (811.11 +/- 89.71 pg ml(-1)) and FSH concentrations (2070 +/- 301.62 pg ml(-1)) decreased to amounts similar to those observed in young cyclic rats. However, plasma concentrations of oestradiol and progesterone were not reduced. In conclusion, the results of the present study indicate that, during ageing, the effect of melatonin is exerted primarily at the hypothalamo-pituitary axis rather than on the ovary. Melatonin restored the basal concentrations of pituitary hormones and pituitary responsiveness to similar values to those observed in young rats.

scholarly journals Ileal transposition helps to regulate plasma hepatokine levels in obese Zucker (Crl:ZUC(ORL)-Leprfa) rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dominika Stygar ◽  
Tomasz Sawczyn ◽  
Agnieszka Dulska ◽  
Elżbieta Chełmecka ◽  
Łukasz Mielańczyk ◽  
...  
Keyword(s):  
Body Weight ◽  
Plasma Levels ◽  
Plasma Concentrations ◽  
The Body ◽  
Retinol Binding Protein ◽  
Fibroblast Growth Factor 21 ◽  
Adult Males ◽  
Total Lipids ◽  
Ileal Transposition ◽  
Sham Surgery

AbstractWe studied the long-term effect of ileal transposition (IT) metabolic surgery on the hepatokines: retinol-binding protein-4 (RBP4), α-2-HS-glycoprotein (aHSG/fetuin-A), and fibroblast growth factor 21 (FGF21), C-reactive protein (CRP) plasma levels, glucose metabolism, body weight, liver histology, as well as total lipids concentration in muscle, liver, and fat tissue of obese Zucker (Crl:ZUC(ORL)-Leprfa) rats. 14 adult males were randomly submitted either to IT or SHAM (control) surgery. Pre-operative hepatokines plasma levels were not significantly different in rats submitted to IT or SHAM protocol. Three months after the procedures the plasma levels of RBP4, aHSG, FGF21, and CRP were significantly lower in IT-operated animals when compared to SHAM-operated group. Three and 12 weeks after the IT and SHAM surgery, the AUCOGTT were significantly lower than AUCOGTT before the surgery. HOMA-IR was lower in rats after IT surgery in comparison to the SHAM-operated rats. Muscle and liver total lipids concentration was reduced after the IT procedure when compared to pre-IT conditions. IT had a significant reductive impact on the body weight in comparison to SHAM surgery in the 4th, 6th, 8th, and 10th week after the surgery. We conclude that IT reduces hepatokines’ plasma concentrations, muscle and liver total lipids concentration but not the inflammatory processes in the liver of Zucker (Crl:ZUC(ORL)-Leprfa) rats.

scholarly journals Influence ofABCC2andABCC4Polymorphisms on Tenofovir Plasma Concentrations in Thai HIV-Infected Patients

2015 ◽  
Vol 59 (6) ◽  
pp. 3240-3245 ◽  
Author(s):  
Kanokrat Rungtivasuwan ◽  
Anchalee Avihingsanon ◽  
Narukjaporn Thammajaruk ◽  
Siwaporn Mitruk ◽  
David M. Burger ◽  
...  
Keyword(s):  
Body Weight ◽  
Multivariate Analysis ◽  
Plasma Concentration ◽  
Protease Inhibitors ◽  
Demographic Data ◽  
Plasma Concentrations ◽  
Multidrug Resistant ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
The Mean

ABSTRACTTenofovir (TFV) is eliminated by renal excretion, which is mediated through multidrug-resistant protein 2 (MRP2) and MRP4, encoded byABCC2andABCC4, respectively. Genetic polymorphisms of these transporters may affect the plasma concentrations of tenofovir. Therefore, the aim of this study was to investigate the influence of genetic and nongenetic factors on tenofovir plasma concentrations. A cross-sectional study was performed in Thai HIV-infected patients aged ≥18 years who had been receiving tenofovir disoproxil fumarate at 300 mg once daily for at least 6 months. A middose tenofovir plasma concentration was obtained. Multivariate analysis was performed to investigate whether there was an association between tenofovir plasma concentrations and demographic data, including age, sex, body weight, estimated glomerular filtration rate (eGFR), hepatitis B virus coinfection, hepatitis C virus coinfection, duration of tenofovir treatment, concomitant use of ritonavir-boosted protease inhibitors, and polymorphisms ofABCC2andABCC4. A total of 150 Thai HIV-infected patients were included. The mean age of the patients was 43.9 ± 7.2 years. The mean tenofovir plasma concentration was 100.3 ± 52.7 ng/ml. In multivariate analysis, a low body weight, a low eGFR, the concomitant use of ritonavir-boosted protease inhibitors, and theABCC44131T → G variation (genotype TG or GG) were independently associated with higher tenofovir plasma concentrations. After adjusting for weight, eGFR, and the concomitant use of ritonavir-boosted protease inhibitors, a 30% increase in the mean tenofovir plasma concentration was observed in patients having theABCC44131 TG or GG genotype. Both genetic and nongenetic factors affect tenofovir plasma concentrations. These factors should be considered when adjusting tenofovir dosage regimens to ensure the efficacy and safety of a drug. (This study has been registered at ClinicalTrials.gov under registration no. NCT01138241.)

scholarly journals Regulation of plasma leptin in mice: influence of age, high-fat diet, and fasting

1997 ◽  
Vol 273 (1) ◽  
pp. R113-R120 ◽  
Author(s):  
B. Ahren ◽  
S. Mansson ◽  
R. L. Gingerich ◽  
P. J. Havel
Keyword(s):  
Body Weight ◽  
Dietary Fat ◽  
High Fat Diet ◽  
Plasma Insulin ◽  
Plasma Concentrations ◽  
Age Groups ◽  
Fat Content ◽  
High Fat ◽  
Background Strain ◽  
Plasma Leptin

Mechanisms regulating circulating leptin are incompletely understood. We developed a radioimmunoassay for mouse leptin to examine the influence of age, dietary fat content, and fasting on plasma concentrations of leptin in the background strain for the ob/ob mouse, the C57BL/6J mouse. Plasma leptin increased with age [5.3 +/- 0.6 ng/ml at 2 mo (n = 23) vs. 14.2 +/- 1.6 ng/ml at 11 mo (n = 15), P < 0.001]. Across all age groups (2-11 mo, n = 160), log plasma leptin correlated with body weight (r = 0.68, P < 0.0001), plasma insulin (r = 0.38, P < 0.001), and amount of intra-abdominal fat (r = 0.90, P < 0.001), as revealed by magnetic resonance imaging. Plasma leptin was increased by a high-fat diet (58% fat for 10 mo) and reduced by fasting for 48 h. The reduction of plasma leptin was correlated with the reduction of plasma insulin (r = 0.43, P = 0.012) but not with the initial body weight or the change in body weight. Moreover, the reduction in plasma leptin by fasting was impaired by high-fat diet. Thus plasma leptin in C57BL/6J mice 1) increases with age or a high-fat diet; 2) correlates with body weight, fat content, and plasma insulin; and 3) is reduced during fasting by an action inhibited by high-fat diet and related to changes of plasma insulin.

Abstract P178: Dairy Consumption and Risk of Becoming Overweight or Obese in Middle-Aged and Older Women.

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Susanne Rautiainen ◽  
Lu Wang ◽  
I-Min Lee ◽  
JoAnn E Manson ◽  
Julie E Buring ◽  
...  
Keyword(s):  
Body Weight ◽  
Dairy Products ◽  
Smoking Status ◽  
Health Study ◽  
High Fat ◽  
Low Fat ◽  
Dairy Intake ◽  
Dairy Consumption ◽  
History Of

Background: Dairy products have been positively associated with weight loss and inversely associated with weight gain. However, limited number of studies has investigated the role of dairy consumption in the prevention of becoming overweight or obese. The aim of this study was to prospectively investigate how consumption of dairy products was associated with the risk of becoming overweight or obese among initially normal-weight women. Methods: We studied 19,180 women aged ≥45y from the Women’s Health Study free of cardiovascular disease (CVD), cancer, and diabetes with an initial body mass index (BMI) of 18.5-<25 kg/m 2 . Dairy intake was assessed through a 131-item food-frequency questionnaire. Total dairy intake was defined as the sum of servings per day of low-fat dairy products (skim/low-fat milk, sherbet, yogurt, and cottage/ricotta cheese) and high-fat dairy products (whole milk, cream, sour cream, ice cream, cream cheese, other cheese, and butter). Women self-reported body weight along with obesity-related risk factors on baseline and annual follow-up questionnaires. In multivariable-adjusted analyses, we included the following covariates: baseline age, randomization treatment, BMI, smoking status, vigorous exercise, postmenopausal status, postmenopausal hormone use, history of hypercholesterolemia, history of hypertension, multivitamin use, alcohol intake, total energy intake, and fruit and vegetable intake. Results: During a mean follow-up of 11.2y (216,979 person-years), 8,582 women became overweight or obese (BMI ≥25 kg/m 2 ). The multivariable-adjusted mean changes in body weight (95% confidence interval (CI)) during the follow-up were 3.9 (3.5-4.3), 3.9 (3.5-4.2), 3.8 (3.5-4.2), 3.7 (3.4-4.1), and 3.4 (3.0-3.7) lbs in quintiles 1-5 of total dairy consumption (P-trend: 0.01), respectively. In multivariable-adjusted analyses (Table 1) , women in the highest versus lowest quintile of had a rate ratio (RR) of 0.91 (0.84-0.98, P-trend: 0.16) of becoming overweight or obese. No associations were observed in highest quintiles of low-fat dairy and high-fat dairy intakes. Conclusion: Greater consumption of dairy products may be inversely ssociated with risk of becoming overweight or obese in women.

scholarly journals Health, body condition and blood metabolites in reindeer after submaintenance feed intake and subsequent feeding

Rangifer ◽  
2000 ◽  
Vol 20 (4) ◽  
pp. 187 ◽  
Author(s):  
A. Nilsson ◽  
Ö. Danell ◽  
M. Murphy ◽  
K. Olsson ◽  
B. Åhman
Keyword(s):  
Body Weight ◽  
Plasma Protein ◽  
Rangifer Tarandus ◽  
Plasma Concentrations ◽  
Experimental Period ◽  
Diet Group ◽  
The Body ◽  
Plasma Metabolites ◽  
Control Group ◽  
Feeding Period

The transition from experimentally induced poor nutritional conditions to feeding was studied with 69 eight-month-old female reindeer (Rangifer tarandus tarandus). During a pre-experimental period, all reindeer were fed a simulated winter diet with 80% lichens Cladina spp. and 20% Vaccinum myrtillus shrubs and Salix spp. leaves (lichen diet) ad lib. The reindeer were divided into five groups. A control group (group C) was fed the lichen diet ad lib. throughout the experiment. Four groups were fed half of that ration for eight days and were then totally deprived of feed for one day (restriction period). During the following 34 days (feeding period) the groups were re-fed the lichen diet (group L), fed pelleted reindeer feed combined with either lichen (group PL) or grass silage (group PS), or fed silage with a gradually increasing addition of pellets (group SP). Weekly measurements of blood samples and body weighr showed that the control group remained clinically healthy and had stable blood plasma concentrations of protein, urea, glucose and insulin throughout the experiment, but they lost weight. At slaughter, before and after the restriction period, all animals had lost rumen-free body weight, but the reindeer fed a restricted amount of feed lost more than the control group. Also the plasma metabolites were affected by the restricted feeding, with increased concentrations of urea and decreased concentrations of glucose. Group L responded immediately to the ad lib. feeding with blood metabolite levels rapidly approaching those of group C. The body weight developments were similar in groups L and C. Although the feed rations were increased gradually, diarrhoea occurred in some animals belonging to groups PL and PS within the first week of the feeding period. All reindeer recovered, after antibiotic treatment of the worst affected animals. The PL and PS groups, which had high contents of metabolisable energy and crude protein in their diets, showed increased con-centtations of plasma protein, urea and insulin. At the end of the feeding period, these groups had increased their body and carcass weights and gained fat, whereas reindeer fed the lichen diet had lost weight. Severe health problems (malnutrition and so-called wet belly) occurred in group SP during the first weeks of feeding and led to loss of animals, and consequently the SP group was excluded from the remainder of rhe experiment. The general conclusion is that the lichen diet did not cause any digestive problems, but resulted in a continuous decline in body weight and small or deficient fat reserves. After the initial diarrhoea, feeding with diets comprising pellets from the start resulted in improved condition, expressed as increased body weight, fat gain and higher concentrations of plasma protein, urea and insulin in relation to the control group. The diet initially based on grass in the form of silage of the given quality seemed insufficient as feed to reindeer calves in a poor nutritional state.

scholarly journals The early changes in retinol-binding protein and prealbumin concentrations in plasma of protein–energy malnourished children after treatment with retinol and an improved diet

1980 ◽  
Vol 43 (3) ◽  
pp. 393-402 ◽  
Author(s):  
Suzanne Large ◽  
G. Neal ◽  
J. Glover ◽  
O. Thanangkul ◽  
R. E. Olson
Keyword(s):  
Body Weight ◽  
Vitamin A ◽  
Nutritional Status ◽  
Plasma Proteins ◽  
Binding Protein ◽  
Vitamin A Deficiency ◽  
Plasma Concentrations ◽  
Retinol Binding Protein ◽  
Mean Values ◽  
The Mean

1. Changes in total retinol-binding protein (RBP), the holoprotein (holoRBP) and prealbumin (PA) concentrations have been monitored in plasma of thirty protein- and vitamin A-deficient preschool children from within a few hours up to 7 weeks after treatment with retinol and a good-quality protein diet.2. The children were classified into groups according to nutritional status as having either kwashiorkor, marasmus-kwashiorkor or marasmus, and given formula diets whose protein and energy contents increased stepwise from 1 g and 105 kJ/kg body-weight respectively up to 4 g and 733 kJ/kg body-weight after 4 weeks. Retinol was administered in the forms of retinyl palmitate either orally or intramuscularly.3. PA and total RBP were determined by electroimmunoassay procedures and the holoRBP by its fluorescence after separation from other plasma proteins.4. RBP in plasma of the vitamin A-deficient child is largely denatured and incapable of binding administered retinol, which must first be taken up by the liver before native holoRBP is released. An increased pool of native apoprotein accumulates in the liver during vitamin A deficiency which is released into plasma quickly after retinol uptake to form peak concentrations of total and holoRBP approximately 3 h after dosing intramuscularly and 6 h orally.5. The accumulated pool of RBP was highest in livers from the marasmus group and lowest in those from the kwashiorkor group, reflecting their relative capacities to synthesize plasma proteins.6. The mean plasma concentrations of total and holoRBP for the various groups were minimal 24–48 h after dosing with retinol and then improved almost linearly over the following week.7. Mean plasma PA concentrations of the various groups on admission were also in order of the severity of their malnutrition. There was little or no change in this protein concentration over the first 24 h after dosing with retinol, but thereafter the mean values rose almost linearly over 2 weeks. Albumin on the other hand changed little during the first week. The results show that PA is the more sensitive measurement of protein nutritional status.

Abstract 15214: Commuting by Public Transportation is Associated With Lower Prevalence of Excess Body Weight, Hypertension, and Diabetes

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Hisako Tsuji ◽  
Ichiro Shiojima
Keyword(s):  
Physical Activity ◽  
Logistic Regression ◽  
Body Weight ◽  
Public Transportation ◽  
Smoking Status ◽  
Excess Body Weight ◽  
Lower Prevalence ◽  
Regression Analyses ◽  
Commuting Mode ◽  
Car Driving

Background: Physical activity reduces body weight and incidence of diabetes mellitus (DM). We examined associations of commuting mode with prevalence of excess body weight, hypertension and DM. Methods: We studied 16,397 subjects who had the annual health checkup offered to adult citizens of Moriguchi city, Osaka, Japan in 2012. The subjects were asked about their work (Is your work physically active, sedentary or "cannot say"?) and commuting mode (walking or cycling / bus or train / car driving). Odds ratios (OR) of prevalence of excess body weight (body mass index >25.0 kg/m 2 ), hypertension, and DM with 95% confidence intervals (CI) relative to the car driving group were calculated using logistic regression analyses adjusted for clinical variables. Results: There were 5,908 eligible workers. Characteristics of the subjects according to commuting mode are presented in the table. Compared to the car driving group, logistic regression analyses showed that the public transportation group had a significantly lower prevalence of excess body weight (OR=0.56, 95% CI=0.45 to 0.69, p<0.0001) after adjustment for basic covariates (age, sex, smoking status, hypercholesterolemia, and physical activity of work) and hypertension, a significantly lower prevalence of hypertension (OR=0.73, 95% CI=0.59 to 0.90, p=0.0035) after adjustment for basic covariates and excess body weight, and a significantly lower prevalence of DM (OR=0.66, 95% CI=0.44 to 0.99, p=0.0427) after adjustment for basic covariates, hypertension, excess body weight, and family history of DM. Conclusions: The use of public transportation was associated with lower prevalence of excess body weight, hypertension, and DM.

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