scholarly journals A Critical Review of the Pharmacokinetics and Pharmacodynamics of Opioid Medications Used in Avian Patients

Birds ◽  
2021 ◽  
Vol 3 (1) ◽  
pp. 1-28
Author(s):  
Evelyn Aliansyah ◽  
Hui Ting Chng ◽  
Shangzhe Xie
Keyword(s):  
Critical Review ◽  
Avian Species ◽  
Pharmacokinetic Data ◽  
Muscovy Duck ◽  
Pharmacokinetics And Pharmacodynamics ◽  
American Kestrel ◽  
Analgesic Effects ◽  
Pavo Cristatus ◽  
Dosing Regimens ◽  
Opioid Medications

Opioid drugs are used to manage moderate to severe pain in mammals and avian species. In dosing opioids for a particular species, it is optimal to use dosing regimens based on pharmacokinetics or pharmacodynamics studies conducted in the same species as variability in the physiology among different species may result in differences in drug pharmacokinetics and pharmacodynamics. Unfortunately, dosing regimens are typically extrapolated from closely related avian species or even mammals, which is unideal. Therefore, this critical review aims to collate and evaluate the dosing regimens of selected opioids: tramadol, hydromorphone, buprenorphine, butorphanol, and fentanyl, in avian species and its related safety, efficacy and pharmacokinetic data. Our review found specific dosing regimens not described in the Exotic Animal Formulary for tramadol used in Indian Peafowl (Pavo cristatus), Muscovy Duck (Cairina moschata) and Hispaniolan Parrot (Amazona ventralis); hydromorphone used in Orange-winged Parrot (Amazona amazonica); buprenorphine used in Cockatiel (Nymphicus hollandicus), American Kestrel (Falco sparverius) and Grey Parrot (Psittacus erithacus); and butorphanol used in Hispaniolan Parrot (Amazona ventralis), Broiler Chicken and Indian Peafowl (Pavo cristatus). Cockatiel appeared to not experience analgesic effects for hydromorphone and buprenorphine, and American Kestrel exhibited sex-dependent responses to opioids. The selected opioids were observed to be generally safe, with adverse effects being dose-dependent.

Pharmacokinetics and Pharmacodynamics of Antistaphylococcal Antibiotics in Continuous Ambulatory Peritoneal Dialysis Patients

1993 ◽  
Vol 13 (2_suppl) ◽  
pp. 367-371 ◽  
Author(s):  
Erich Keller
Keyword(s):  
Peritoneal Dialysis ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Inhibitory Concentration ◽  
Pharmacokinetic Data ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Antistaphylococcal Activity ◽  
Cure Rates ◽  
Vitro Data ◽  
In Vitro Data

Staphylococci are the leading pathogens In continuous ambulatory peritoneal dialysis (CAPD)-related peritonitis. Vancomycin appears to be an outstanding antistaphylococcal drug because resistance to It Is nearly absent. The pharmacokinetics of vancomycin and clinical cure rates of peritonitis with different dosing guidelines have been studied extensively. Different dosing guidelines with IP or IV loading doses followed or not followed by IP maintenance doses are used successfully, despite the fact that some of the dosing schemes produce apparently suboptimal drug levels referring to In vitro data like the MIC value (minimum Inhibitory concentration). Alternatively, amlnoglycosldes, cephalosporlns, Isoxazolyl penicillins, and broad-spectrum penicillins combined with betalactamase Inhibitors may be used for the treatment of gram-positive peritonitis. For the above panicillins pharmacokinetic data are scarce, and clinical experience is limited. Rifampin has excellent Intracellular antistaphylococcal activity and should be used In combination with other antibiotics. Although pharmacokinetic data are lacking, rifampin dosages do not require adaptation to renal function or replacement therapy.

scholarly journals Comparison of Pharmacokinetics and Safety of Voriconazole Intravenous-to-Oral Switch in Immunocompromised Adolescents and Healthy Adults

2011 ◽  
Vol 55 (12) ◽  
pp. 5780-5789 ◽  
Author(s):  
Timothy A. Driscoll ◽  
Haydar Frangoul ◽  
Eneida R. Nemecek ◽  
Donald K. Murphey ◽  
Lolie C. Yu ◽  
...  
Keyword(s):  
Body Weight ◽  
Steady State ◽  
Oral Treatment ◽  
Area Under The Curve ◽  
Pharmacokinetic Data ◽  
Young Adolescents ◽  
Dosing Regimens ◽  
Oral Switch ◽  
To Receive ◽  
Higher Doses

ABSTRACTThe current voriconazole dosing recommendation in adolescents is based on limited efficacy and pharmacokinetic data. To confirm the appropriateness of dosing adolescents like adults, a pharmacokinetic study was conducted in 26 immunocompromised adolescents aged 12 to <17 years following intravenous (IV) voriconazole to oral switch regimens: 6 mg/kg IV every 12 h (q12h) on day 1 followed by 4 mg/kg IV q12h, then switched to 300 mg orally q12h. Area under the curve over a 12-hour dosing interval (AUC0–12) was calculated using a noncompartmental method and compared to the value for adults receiving the same dosing regimens. On average, the AUC0–12in adolescents after the first loading dose on day 1 and at steady state during IV treatment were 9.14 and 22.4 μg·h/ml, respectively (approximately 34% and 36% lower, respectively, than values for adults). At steady state during oral treatment, adolescents also had lower average exposure than adults (16.7 versus 34.0 μg·h/ml). Larger intersubject variability was observed in adolescents than in adults. There was a slight trend for some young adolescents with low body weight to have lower voriconazole exposure. It is likely that these young adolescents may metabolize voriconazole more similarly to children than to adults. Overall, with the same dosing regimens, voriconazole exposures in the majority of adolescents were comparable to those in adults. The young adolescents with low body weight during the transitioning period from childhood to adolescence (e.g., 12 to 14 years old) may need to receive higher doses to match the adult exposures. Safety of voriconazole in adolescents was consistent with the known safety profile of voriconazole.

scholarly journals Ceftolozane/Tazobactam Dosing Requirements Against Pseudomonas aeruginosa Bacteremia

Dose-Response ◽  
2020 ◽  
Vol 18 (1) ◽  
pp. 155932581988579
Author(s):  
Jesus Ruiz ◽  
Alejandra Ferrada ◽  
Miguel Salavert ◽  
Mónica Gordon ◽  
Esther Villarreal ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Renal Clearance ◽  
Pharmacokinetic Data ◽  
Limit Values ◽  
Beta Lactamases ◽  
Susceptibility Data ◽  
A Value ◽  
Dosing Regimens ◽  
Different Doses ◽  
Mic Value

Objectives: To assess the probability of reaching adequate pharmacokinetic/pharmacodynamics values for ceftolozane/tazobactam at different doses and degrees of renal functions in patients with Pseudomonas aeruginosa bacteremia. Methods: Six dosing regimens were evaluated: 0.5/0.25 g, 1/0.5 g, and 2/1 g every 8 hours given as 1 hour or 3 hours infusions. Pharmacokinetic data were obtained from the literature. Susceptibility data to ceftolozane were collected from patients with P aeruginosa infection treated with ceftolozane-tazobactam. Probability of reaching a fraction of time (fT) >40% minimum inhibitory concentration (MIC) and fT >100%MIC value for ceftolozane at 3 different renal clearance values was evaluated. For tazobactam, the probability of reaching an fT >40% and >70% for 3 limit values was calculated. Results: Thirty-seven strains were included. For ceftolozane, the probability of reaching a fT >40%MIC was greater than 90% for any degree of renal function. The probability of reaching a fT >100%MIC for 1 g dose infused over 1 hour and 3 hours was 82.2% and 86.4% for a creatinine clearance (ClCr) >90 mL/min. Using a 2 g dose, the probability was greater than 90% for both infusions rates. For tazobactam, the probability of reaching a value of fT >50% of the limit concentrations was greater than 90% for a ClCr of 70 mL/min. In the case of a ClCr >90 mL/min and limit concentration values ≥ 0.25 mg/mL, only extended infusions showed a probability >90%. Conclusions and Relevance: The standard doses of ceftolozane/tazobactam achieve an adequate fT >40%MIC value. However, doses of 2 g in extended infusion is necessary to reach a value of fT >100%MIC, especially in patients with an increased renal clearance and high levels of beta-lactamases expression.

scholarly journals Pharmacokinetic Data Are Predictive ofIn VivoEfficacy for Cefixime and Ceftriaxone against Susceptible and ResistantNeisseria gonorrhoeaeStrains in the Gonorrhea Mouse Model

2019 ◽  
Vol 63 (3) ◽  
Author(s):  
Kristie L. Connolly ◽  
Ann E. Eakin ◽  
Carolina Gomez ◽  
Blaire L. Osborn ◽  
Magnus Unemo ◽  
...  
Keyword(s):  
Single Dose ◽  
Mouse Model ◽  
Infection Model ◽  
Pharmacokinetic Data ◽  
Drug Resistant ◽  
Genital Tract Infection ◽  
Clear Dose Response ◽  
Dosing Regimens ◽  
Strain Fa1090

ABSTRACTThere is a pressing need for drug development for gonorrhea. Here we describe a pharmacokinetic (PK)/pharmacodynamic (PD) analysis of extended-spectrum cephalosporins (ESC) against drug-susceptible and drug-resistant gonococcal strains in a murine genital tract infection model. The PK determined in uninfected mice displayed a clear dose-response in plasma levels following single doses of ceftriaxone (CRO) (intraperitoneal) or cefixime (CFM) (oral). The observed doses required for efficacy against ESC-susceptible (ESCs) strain FA1090 were 5 mg/kg of body weight (CRO) and 12 mg/kg (CFM); these doses had estimated therapeutic times (the time that the free drug concentration remains above the MIC [fTMIC]) of 24 h and 37 h, respectively. No single dose of CRO or CFM was effective against ESC-resistant (ESCr) strain H041. However, fractionation (three times a day every 8 h [TIDq8h]) of a 120-mg/kg dose of CRO resulted in estimated therapeutic times in the range of 23 h and cleared H041 infection in a majority (90%) of mice, comparable to the findings for gentamicin. In contrast, multiple CFM doses of 120 or 300 mg/kg administered TIDq8h cleared infection in ≤50% of mice, with the therapeutic times estimated from single-dose PK data being 13 and 27 h, respectively. This study reveals a clear relationship between plasma ESC levels and bacterial clearance rates in the gonorrhea mouse model. The PK/PD relationships observed in mice reflected those observed in humans, within vivoefficacy against an ESCsstrain requiring doses that yielded anfTMICin excess of 20 to 24 h. PK data also accurately predicted the failure of single doses of ESCs against an ESCrstrain and were useful in designing effective dosing regimens.

Pharmacokinetics and pharmacodynamics of six epoetin alfa dosing regimens in anemic critically ill patients without acute blood loss*

2009 ◽  
Vol 37 (4) ◽  
pp. 1299-1307 ◽  
Author(s):  
Alejandro C. Arroliga ◽  
Kalpatha K. Guntupalli ◽  
Jessica S. Beaver ◽  
Wayne Langholff ◽  
Kimberly Marino ◽  
...  
Keyword(s):  
Blood Loss ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Acute Blood Loss ◽  
Epoetin Alfa ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Dosing Regimens

Explaining Interindividual Variability of Docetaxel Pharmacokinetics and Pharmacodynamics in Asians Through Phenotyping and Genotyping Strategies

2002 ◽  
Vol 20 (17) ◽  
pp. 3683-3690 ◽  
Author(s):  
Boon-Cher Goh ◽  
Soo-Chin Lee ◽  
Ling-Zhi Wang ◽  
Lu Fan ◽  
Jia-Yi Guo ◽  
...  
Keyword(s):  
Interindividual Variability ◽  
Performance Status ◽  
Regulatory Region ◽  
Area Under The Curve ◽  
Serum Levels ◽  
Pharmacokinetic Data ◽  
Data Sets ◽  
Pharmacokinetics And Pharmacodynamics ◽  
C3435t Polymorphism ◽  
And Performance

PURPOSE: To explain the variability of docetaxel pharmacokinetics through study of CYP3A phenotype and genotype, and MDR1 genotype. PATIENTS AND METHODS: We studied the pharmacokinetics and pharmacodynamics of docetaxel in patients in whom it was indicated and who had not received known CYP3A4 substrates. Midazolam was administered intravenously to these patients at least 2 days before docetaxel treatment, and systemic clearances of both drugs were correlated. Patients were characterized for polymorphisms in the CYP3A4 promoter region, CYP3A5, and the C3435T polymorphism of MDR1. RESULTS: Thirty-two patients were enrolled, of whom 31 had full pharmacokinetic data sets. Docetaxel clearance correlated with midazolam clearance, body-surface area, serum albumin, and performance status. Docetaxel and midazolam clearances were normally distributed. In multiple linear regression analyses, midazolam clearance and performance status were the only significant covariates of docetaxel clearance, and the area under the curve of docetaxel, serum levels of alpha-1-acid glycoprotein, and ALT were significant predictors of nadir neutrophil count. No polymorphisms were detected in the 5′ regulatory region of CYP3A4. Nine patients of 25 studied were homozygous for the CYP3A5*3 genotype, and had lower mean clearance of midazolam but not docetaxel. The T/T genotype at the C3435T of MDR1, which is associated with reduced P-glycoprotein function, was found in eight of 27 patients. CONCLUSION: Midazolam may be used as a probe drug for CYP3A activity to predict docetaxel clearances, hence reducing interindividual variability. Homozygotes for CYP3A5*3 and C3435T of MDR1 are common in our population, and their effects on pharmacokinetics of relevant substrates should be studied further.

scholarly journals Population Pharmacokinetics and Pharmacodynamics of Extended-Infusion Piperacillin and Tazobactam in Critically Ill Children

2015 ◽  
Vol 60 (1) ◽  
pp. 522-531 ◽  
Author(s):  
Kristen Nichols ◽  
Eun Kyoung Chung ◽  
Chad A. Knoderer ◽  
Lauren E. Buenger ◽  
Daniel P. Healy ◽  
...  
Keyword(s):  
Steady State ◽  
Population Pharmacokinetics ◽  
Critically Ill ◽  
Critically Ill Children ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Data ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Study Objective ◽  
Population Pharmacokinetics And Pharmacodynamics ◽  
Extended Infusion

ABSTRACTThe study objective was to evaluate the population pharmacokinetics and pharmacodynamics of extended-infusion piperacillin-tazobactam in children hospitalized in an intensive care unit. Seventy-two serum samples were collected at steady state from 12 patients who received piperacillin-tazobactam at 100/12.5 mg/kg of body weight every 8 h infused over 4 h. Population pharmacokinetic analyses were performed using NONMEM, and Monte Carlo simulations were performed to estimate the piperacillin pharmacokinetic profiles for dosing regimens of 80 to 100 mg/kg of the piperacillin component given every 6 to 8 h and infused over 0.5, 3, or 4 h. The probability of target attainment (PTA) for a cumulative percentage of the dosing interval that the drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (TMIC) of ≥50% was calculated at MICs ranging from 0.25 to 64 mg/liter. The mean ± standard deviation (SD) age, weight, and estimated glomerular filtration rate were 5 ± 3 years, 17 ± 6.2 kg, and 118 ± 41 ml/min/1.73 m2, respectively. A one-compartment model with zero-order input and first-order elimination best fit the pharmacokinetic data for both drugs. Weight was significantly associated with piperacillin clearance, and weight and sex were significantly associated with tazobactam clearance. Pharmacokinetic parameters (mean ± SD) for piperacillin and tazobactam were as follows: clearance, 0.22 ± 0.07 and 0.19 ± 0.07 liter/h/kg, respectively; volume of distribution, 0.43 ± 0.16 and 0.37 ± 0.14 liter/kg, respectively. All extended-infusion regimens achieved PTAs of >90% at MICs of ≤16 mg/liter. Only the 3-h infusion regimens given every 6 h achieved PTAs of >90% at an MIC of 32 mg/liter. For susceptible bacterial pathogens, piperacillin-tazobactam doses of ≥80/10 mg/kg given every 8 h and infused over 4 h achieve adequate pharmacodynamic exposures in critically ill children.

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