scholarly journals Tylosin Dosage Adjustment Based on Allometric Scaling in Male Turkeys

Antibiotics ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1057
Author(s):  
Błażej Poźniak ◽  
Marta Tikhomirov ◽  
Kamila Bobrek ◽  
Paweł Jajor ◽  
Marcin Świtała
Keyword(s):  
High Performance ◽  
Allometric Scaling ◽  
Interindividual Variability ◽  
Dosage Adjustment ◽  
Age Groups ◽  
Area Under The Curve ◽  
Internal Exposure ◽  
Age Dependent ◽  
Non Linear ◽  
Selection For

Turkeys’ body weight (BW) increases 10-fold within only 2.5 months, leading to a change in the pharmacokinetics (PK) of drugs according to allometric principles. Thus, the same dosage may lead to age-dependent variability in efficacy, in particular, to treatment failure and/or selection for resistance. The study aimed to investigate whether a non-linear dosage based on a published allometric model for tylosin clearance, may optimize the internal exposure in growing turkeys. The single dose PK study was performed on turkeys aged 6, 9.5, 13 and 17 weeks (BW from 1.75 kg to 15.75 kg). Tylosin was administered intravenously (i.v.) or orally (p.o.) according to following protocols: Dose = 31.6 × BW0.58 or Dose = 158 × BW0.58, respectively. Plasma tylosin was measured using high-performance liquid chromatography and non-compartmental PK analysis was performed. The area under the curve (AUClast) after i.v. administration was 8.90 ± 1.01; 7.51 ± 1.11; 6.54 ± 1.20 and 8.01 ± 1.75 mg × h/L in 6-; 9.5-; 13- and 17-week-old turkeys, respectively. After p.o. administration AUClast was 4.80 ± 2.92; 4.60 ± 2.45; 3.00 ± 1.49 and 3.24 ± 2.00 mg × h/L in respective age groups indicating high variability. For i.v. administration, the non-linear dosage allowed to minimize the age-dependent variability in AUC. However, due to low oral bioavailability (8–12%) and resulting interindividual variability, the proposed approach may not improve tylosin efficacy in turkeys under farm conditions.

scholarly journals Population Pharmacokinetics of Amphotericin B Lipid Complex in Neonates

2005 ◽  
Vol 49 (12) ◽  
pp. 5092-5098 ◽  
Author(s):  
Gudrun Würthwein ◽  
Andreas H. Groll ◽  
Georg Hempel ◽  
Felice C. Adler-Shohet ◽  
Jay M. Lieberman ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Gestational Age ◽  
High Performance ◽  
Interindividual Variability ◽  
Age Groups ◽  
Compartment Model ◽  
Multicenter Trial ◽  
Volume Of Distribution ◽  
Lipid Complex ◽  
Amphotericin B Lipid Complex

ABSTRACT The pharmacokinetics of amphotericin B lipid complex (ABLC) were investigated in neonates with invasive candidiasis enrolled in a phase II multicenter trial. Sparse blood (153 samples; 1 to 9 per patient, 1 to 254 h after the dose) and random urine and cerebrospinal fluid (CSF) samples of 28 neonates (median weight [WT], 1.06 kg; range, 0.48 to 4.9 kg; median gestational age, 27 weeks; range, 24 to 41 weeks) were analyzed. Patients received intravenous ABLC at 2.5 (n = 15) or 5 (n = 13) mg/kg of body weight once a day over 1 or 2 h, respectively, for a median of 21 days (range, 4 to 47 days). Concentrations of amphotericin B were quantified as total drug by high-performance liquid chromatography. Blood data for time after dose (TAD) of <24 h fitted best to a one-compartment model with an additive-error model for residual variability, WT0.75 (where 0.75 is an exponent) as a covariate of clearance (CL), and WT as a covariate of volume of distribution (V). Prior amphotericin B, postnatal age, and gestational age did not further improve the model. The final model equations were CL (liters/h) = 0.399 × WT0.75 (interindividual variability, 35%) and V (liters) = 10.5 × WT (interindividual variability, 43%). Noncompartmental analysis of pooled data with a TAD of >24 h revealed a terminal half-life of 395 h. Mean concentrations in the urine after 1, 2, and 3 weeks ranged from 0.082 to 0.430 μg/ml, and those in CSF ranged from undetectable to 0.074 μg/ml. The disposition of ABLC in neonates was similar to that observed in other age groups: weight was the only factor that influenced clearance. Based on these results and previously published safety and efficacy data, we recommend a daily dosage between 2.5 and 5.0 mg/kg for treatment of invasive Candida infections in neonates.

Reference ranges of serum bile acids in children and adolescents

2015 ◽  
Vol 53 (11) ◽  
Author(s):  
Jörg Jahnel ◽  
Evelyn Zöhrer ◽  
Hubert Scharnagl ◽  
Wolfgang Erwa ◽  
Günter Fauler ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Children And Adolescents ◽  
Bile Acids ◽  
High Performance ◽  
High Resolution Mass Spectrometry ◽  
Age Groups ◽  
Reference Ranges ◽  
Healthy Children ◽  
Age Dependent ◽  
Resolution Mass

AbstractBile acids (BA) are found predominantly in bile but also in serum, where they can be used as markers for inborn and acquired hepatobiliary disorders. We measured serum BA levels by mass spectrometry to determine reference ranges for healthy children and adolescents in different age groups.In 194 healthy children and adolescents (0–19 years) concentrations of serum BA and BA composition were determined using high-performance liquid chromatography high-resolution mass spectrometry. Individuals were classified by ages into five groups: 0–5 months, 6–24 months, 3–5 years, 6–11 years, and >11 years.The 95% confidence interval of serum total BA values in newborns was 3.85–6.32 μmol/L. In the cohort aged 6–24 months total BA values were significantly higher (6.61–9.43 μmol/L; p<0.001). During growth, values decreased (6–11 years; 3.61–5.41 μmol/L), and after 11 years (3.09–4.12 μmol/L) resembled those in adults (0.28–6.50 μmol/L). With respect to conjugation patterns, in neonates BA were primarily conjugated with taurine; however, after 6 months glycine conjugates clearly predominated.: Our data show that serum BA values vary substantially during the first years of life and that reference ranges for BA are age-dependent. The physiologic mechanisms underlying these variations remain to be determined.

A Comparison of the Pharmacokinetics and Tolerability of the Anti-Migraine Compound Almotriptan in Healthy Adolescents and Adults

Cephalalgia ◽  
2004 ◽  
Vol 24 (4) ◽  
pp. 288-292 ◽  
Author(s):  
JR Baldwin ◽  
JC Fleishaker ◽  
NE Azie ◽  
BJ Carel
Keyword(s):  
High Performance ◽  
Age Groups ◽  
Area Under The Curve ◽  
Pharmacokinetic Parameters ◽  
Lower Body ◽  
Compartment Analysis ◽  
Lower Body Weight ◽  
Adolescents And Adults ◽  
Two Populations ◽  
Two Age Groups

This study was designed to assess and compare the pharmacokinetics and tolerability of almotriptan, a 5-HT1B/1D agonist used to treat migraine attacks, in adolescents and adults. Healthy adolescents ( n = 18) and adults ( n = 18) received a single 12.5-mg dose of almotriptan after fasting overnight. Plasma and urinary almotriptan concentrations were measured by high-performance liquid chromatography. Pharmacokinetic parameters of almotriptan were determined by non-compartment analysis. The 90% confidence interval (CI) approach was employed to assess age effects. Mean Cmax, tmax, area under the curve (AUC 0-∞), half-life, and percentage excreted in urine were nearly identical for the two populations. Mean oral (CLPO) and renal (CLR) clearances were similar between the age groups; however, weight-corrected CLPO was approximately 32% higher (90% CI 16, 51) in adolescents compared with adults. The higher weight-corrected CLPO appeared to offset increases in exposure expected on the basis of lower body weight in adolescents. The findings were the same when a subgroup ( n = 9) of 12-14-year old children was compared with adults. The type, incidence and severity of adverse events were similar between the two age groups and were consistent with those reported previously during adult clinical trials. Based on these pharmacokinetic and tolerability findings, no dose adjustment for almotriptan would be required when treating patients as young as 12 years old.

scholarly journals Safety and Single-Dose Pharmacokinetics of Abacavir (1592U89) in Human Immunodeficiency Virus Type 1-Infected Children

1999 ◽  
Vol 43 (3) ◽  
pp. 609-615 ◽  
Author(s):  
Walter Hughes ◽  
James A. McDowell ◽  
Jerry Shenep ◽  
Patricia Flynn ◽  
Mark W. Kline ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Body Weight ◽  
High Performance ◽  
Age Groups ◽  
Area Under The Curve ◽  
Oral Solution ◽  
Parameter Estimates ◽  
Immunodeficiency Virus ◽  
The Mean

ABSTRACT Abacavir (formerly 1592U89) is a potent 2′-deoxyguanosine analog reverse transcriptase inhibitor that has been demonstrated to have a favorable safety profile in initial clinical trials with adults with human immunodeficiency virus (HIV) type 1 infection. A phase I study was conducted to evaluate the pharmacokinetics and safety of abacavir following the administration of two single oral doses (4 and 8 mg/kg of body weight) to 22 HIV-infected children ages 3 months to 13 years. Plasma was collected for analysis at predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, and 8 h after the administration of each dose. Plasma abacavir concentrations were determined by high-performance liquid chromatography, and data were analyzed by noncompartmental methods. Abacavir was well tolerated by all subjects. The single abacavir-related adverse event was rash, which occurred in 2 of 22 subjects. After administration of the oral solution, abacavir was rapidly absorbed, with the time to the peak concentration in plasma occurring within 1.5 h postdosing. Pharmacokinetic parameter estimates were comparable among the different age groups for each dose level. The mean maximum concentration in plasma (C max) and the mean area under the curve from time zero to infinity (AUC0–∞) increased by 16 and 45% more than predicted, respectively, as the abacavir dose was doubled from 4 to 8 mg/kg (C max increased from 1.69 to 3.94 μg/ml, and AUC0–∞ increased from 2.82 to 8.09 μg · h/ml). Abacavir was rapidly eliminated, with a mean elimination half-life of 0.98 to 1.13 h. The mean apparent clearance from plasma decreased from 27.35 to 18.88 ml/min/kg as the dose increased. Neither body surface area nor creatinine clearance were correlated with pharmacokinetic estimates at either dose. The extent of exposure to abacavir appears to be slightly lower in children than in adults, with the comparable unit doses being based on body weight. In conclusion, this study showed that abacavir is safe and well tolerated in children when it is administered as a single oral dose of 4 or 8 mg/kg.

scholarly journals Allometric Optimization of Enrofloxacin Dosage in Growing Male Turkeys: Empirical Evidence for Improved Internal Exposure

Antibiotics ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 925
Author(s):  
Błażej Poźniak ◽  
Marta Tikhomirov ◽  
Karolina Motykiewicz-Pers ◽  
Kamila Bobrek ◽  
Marcin Świtała
Keyword(s):  
Age Groups ◽  
Major Change ◽  
Antimicrobial Effect ◽  
Internal Exposure ◽  
Oral Drug ◽  
Rapid Weight Gain ◽  
Time Curve ◽  
Age Related ◽  
Non Linear ◽  
Allometric Relation

Rapid weight gain in turkeys causes a major change in the pharmacokinetics of drugs, leading to age-dependent variability in the internal exposure and, possibly, treatment failure and/or selection for antimicrobial resistance in young individuals. The aim of the study was to investigate whether a non-linear dosing protocol that accounts for the previously established allometric relation between enrofloxacin clearance and body weight (BW) may optimize the internal exposure to enrofloxacin in growing male turkeys. Enrofloxacin was administered four times, between the age of 5 and 16.5 weeks, when the turkeys’ BW increased from 1.47 to 14.92 kg. Enrofloxacin was given intravenously (i.v.) or orally at the dose calculated as follows: Dose = 30 × BW0.59. After i.v. administration, the internal exposure to the drug—quantified as the area under the concentration–time curve (AUC)—was showing little age-related variation. The coefficient of variation (CV) for AUC in all individuals (15.7%) was only slightly higher than within the age groups (5.4–13.7%). After oral drug administration, CV for AUC in all individuals (22.1%) was similar as within the age groups (8.7–32.2%). These results show that intra-species allometric scaling may be efficiently implemented in the non-linear approach to enrofloxacin dosage in turkeys in order to obtain a precise internal exposure for the optimal antimicrobial effect.

COVID - 19 AND THE PROBLEM OF PERSONALITY

2020 ◽  
pp. 31-35
Author(s):  
Mazaeva N.A. ◽  
Golovina A.G.
Keyword(s):  
General Population ◽  
Age Groups ◽  
Personal Transformation ◽  
Personality Changes ◽  
Age Dependent

In order to determine possible trends in the dynamics and characterological structure of personality in the General population caused by the COVID-19 pandemic, which is a long-term strong stressful effect and clinically and psychopathologically comparable to chronic personality changes after experiencing a disaster, the conditions predisposing to personal transformation, including clinical and prognostic patterns, are analyzed. The age-dependent nature of these changes is shown, and a number of features identified for different age groups are discussed.

scholarly journals Sphingolipid Analysis Indicate Lactosylceramide as a Potential Biomarker of Inflammatory Bowel Disease in Children

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1083
Author(s):  
Aleksandra Filimoniuk ◽  
Agnieszka Blachnio-Zabielska ◽  
Monika Imierska ◽  
Dariusz Marek Lebensztejn ◽  
Urszula Daniluk
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
High Performance ◽  
Area Under The Curve ◽  
Study Groups ◽  
Diagnostic Value ◽  
Serum Samples ◽  
Specificity And Sensitivity ◽  
Potential Biomarker ◽  
Inflammatory Bowel

An altered ceramide composition in patients with inflammatory bowel disease (IBD) has been reported recently. The aim of this study was to evaluate the concentrations of sphingolipids in the serum of treatment-naive children with newly diagnosed IBD and to determine the diagnostic value of the tested lipids in pediatric IBD. The concentrations of sphingolipids in serum samples were evaluated using a quantitative method, an ultra-high-performance liquid chromatography-tandem mass spectrometry in children with Crohn’s disease (CD) (n=34), ulcerative colitis (UC) (n = 39), and controls (Ctr) (n = 24). Among the study groups, the most significant differences in concentrations were noted for C16:0-LacCer, especially in children with CD compared to Ctr or even to UC. Additionally, the relevant increase in C20:0-Cer and C18:1-Cer concentrations were detected in both IBD groups compared to Ctr. The enhanced C24:0-Cer level was observed only in UC, while C18:0-Cer only in the CD group. The highest area under the curve (AUC), specificity, and sensitivity were determined for C16:0-LacCer in CD diagnosis. Our results suggest that the serum LacC16-Cer may be a potential biomarker that distinguishes children with IBD from healthy controls and differentiates IBD subtypes. In addition, C20:0-Cer and C18:0-Cer levels also seem to be closely connected with IBD.

scholarly journals Age-related decline in the taurine content of the skin in rodents

Amino Acids ◽  
2021 ◽  
Author(s):  
Tomohisa Yoshimura ◽  
Yuki Inokuchi ◽  
Chikako Mutou ◽  
Takanobu Sakurai ◽  
Tohru Nagahama ◽  
...  
Keyword(s):  
High Performance ◽  
Age Groups ◽  
Immunohistochemical Analysis ◽  
Sprague Dawley ◽  
Taurine Supplementation ◽  
Hairless Mice ◽  
Age Related ◽  
Sprague Dawley Rats ◽  
High Concentrations ◽  
Effects Of Aging

AbstractTaurine, a sulfur-containing amino acid, occurs at high concentrations in the skin, and plays a role in maintaining the homeostasis of the skin. We investigated the effects of aging on the content and localization of taurine in the skin of mice and rats. Taurine was extracted from the skin samples of hairless mice and Sprague Dawley rats, and the taurine content of the skin was determined by high-performance liquid chromatography (HPLC). The results of the investigation revealed that the taurine content in both the dermis and epidermis of hairless mice declined significantly with age. Similar age-related decline in the skin taurine content was also observed in rats. In contrast, the taurine content in the sole remained unchanged with age. An immunohistochemical analysis also revealed a decreased skin taurine content in aged animals compared with younger animals, although no significant differences in the localization of taurine were observed between the two age groups. Supplementation of the drinking water of aged mice with 3% (w/v) taurine for 4 weeks increased the taurine content of the epidermis, but not the dermis. The present study showed for the first time that the taurine content of the skin decreased with age in mice and rats, which may be related to the impairment of the skin homeostasis observed with aging. The decreased taurine content of the epidermis in aged animals was able to be rescued by taurine supplementation.

scholarly journals Alpha Spectrometry of Radon Short-Lived Progeny in Drinking Water and Assessment of the Public Effective Dose: Results from the Cilento Area, Province of Salerno, Southern Italy

Materials ◽  
2020 ◽  
Vol 13 (24) ◽  
pp. 5840
Author(s):  
Enver Faella ◽  
Simona Mancini ◽  
Michele Guida ◽  
Albina Cuomo ◽  
Domenico Guida
Keyword(s):  
Drinking Water ◽  
Effective Dose ◽  
Health Hazard ◽  
Age Groups ◽  
Internal Exposure ◽  
Threshold Values ◽  
Campania Region ◽  
Radon Activity ◽  
National Regulation ◽  
South Italy

Radon is a naturally occurring radioactive gas present in the hydrosphere, lithosphere and atmosphere abundantly. Its ionizing radiation provides the largest human internal exposure by inhalation and ingestion to natural sources, constituting a serious health hazard. The contribution to total exposure is mainly due to inhalation, as ingestion by food or drinking water is typically very small. However, because of public health concerns, the contributions from all these sources are limited by regulations and remedial action should be taken in the event that the defined threshold values are overcome. In this paper, the first campaign of measurements to control the radon activity concentration in drinking water from public water supplies in the province of Salerno, south Italy, is described. The results represent a main reference for the area, as it was never investigated before. The purpose of this survey was to contribute to data compilation concerning the presence of radon-222 in groundwater in the Campania region and to determine the associated risk for different age groups. The maximum radon activity concentrations and the related total annual public effective dose turned out to be lower than the threshold values (100 Bq/l and 0.1 mSv/y, respectively) indicated by international guidelines and the national regulation, showing that the health risks for public consumption can be considered negligible.

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