scholarly journals Plasma levels of a methadone constant rate infusion and their corresponding effects on thermal and mechanical nociceptive thresholds in dogs

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
T. Amon ◽  
S. B. R. Kästner ◽  
M. Kietzmann ◽  
J. Tünsmeyer
Keyword(s):  
Plasma Concentrations ◽  
Isotonic Saline ◽  
Volume Of Distribution ◽  
Pharmacokinetic Data ◽  
Thermal Thresholds ◽  
Treatment Groups ◽  
Mechanical Threshold ◽  
Constant Rate ◽  
Healthy Dogs ◽  
Rate Infusion

Abstract Background The present study aimed to collect pharmacokinetic data of a methadone continuous rate infusion (CRI) and to investigate its effect on mechanical and thermal nociceptive thresholds. Seven, 47 to 54 months old beagle dogs, weighing 9.8 to 21.2 kg, were used in this experimental, randomized, blinded, placebo-controlled crossover study. Each dog was treated twice with either a methadone bolus of 0.2 mg kg− 1 followed by a 0.1 mg kg− 1 h− 1 methadone CRI (group M) or an equivalent volume of isotonic saline solution (group P) for 72 h. Mechanical and thermal thresholds, as well as vital parameters and sedation were measured during CRI and for further 24 h. Blood samples for methadone plasma concentrations were collected during this 96 h period. Results Percentage thermal excursion (%TE) increased significantly from baseline (BL) until 3 h after discontinuation of CRI in M. Within P and between treatment groups differences were not significant. Mechanical threshold (MT) increased in M until 2 h after CRI discontinuation. Bradycardia and hypothermia occurred in M during drug administration and dogs were mildly sedated for the first 47 h. Decreased food intake and regurgitation were observed in M in five and four dogs, respectively. For methadone a volume of distribution of 10.26 l kg− 1 and a terminal half-life of 2.4 h were detected and a clearance of 51.44 ml kg− 1 min− 1 was calculated. Effective methadone plasma concentrations for thermal and mechanical antinociception were above 17 ng ml− 1. Conclusion A methadone CRI of 0.1 mg kg− 1 h− 1 for 3 days after a loading dose results in steady anti-nociceptive effects in an acute pain model in healthy dogs. Main side effects were related to gastrointestinal tract, hypothermia, bradycardia and sedation.

Pharmacokinetic Evaluation of anti-HIV Drug Interactions: Effect of Zidovudine on 2′-3′-Dideoxyinosine Kinetics in Monkeys

1993 ◽  
Vol 4 (3) ◽  
pp. 155-159 ◽  
Author(s):  
M. Qian ◽  
A. R. Swagler ◽  
M. Mehta ◽  
C.T. Vishwanathan ◽  
J. M. Gallo
Keyword(s):  
Dose Group ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
High Dose ◽  
Combination Regimen ◽  
Time Profiles ◽  
Elimination Half ◽  
Constant Rate ◽  
Rate Infusion

The current investigation was conducted to determine if zidovudine (AZT) altered the pharmacokinetics of dideoxyinosine (ddl) in non-hurnan primates, an appropriate animal model for AZT and ddl pharmacokinetics in human. Each of nine animals received 20 mg kg−1 of ddl intravenously in the absence and presence of two different dosage regimens of AZT. For each combination regimen, AZT was administered as a combined i.v. bolus-constant rate infusion regimen for 30 min that produced AZT plasma concentrations of about 4 μg ml−1 in six animals (low dose group) and 11 μg ml−1 in three others (high dose group). Serial blood samples were collected, and pharmacokinetic parameters for ddl were calculated based on plasma ddl concentrations measured by HPLC techniques. The pharmacokinetics of ddl given alone in the first phase of the low ( n = 6) and high ( n = 6) dose AZT groups, resulted in a mean elimination half-life 1.54 and 1.9h, a mean total clearance of 0.62 and 0.731 h−1 kg−1, and a mean steady state volume of distribution of 1.02 and 0.891 kg−1, respectively. Following combined ddl and AZT administrations, in both the low and high dose AZT groups, plasma concentration-time profiles of ddl were similar for each monkey, and no statistical differences were observed in the pharmacokinetic parameters compared to those obtained when ddl was given alone. The fact that AZT does not alter the pharmacokinetics of ddl at the range of AZT dose studied provides a basis for rational dosage design for combined ddl and AZT treatments in HIV infection.

scholarly journals The intravenous pharmacokinetics of diminazene in healthy dogs

2009 ◽  
Vol 80 (4) ◽  
Author(s):  
V. Naidoo ◽  
M.S.G. Mulders ◽  
G.E. Swan
Keyword(s):  
Plasma Concentrations ◽  
Compartmental Analysis ◽  
Central Compartment ◽  
Volume Of Distribution ◽  
Time Profile ◽  
Secondary Peak ◽  
German Shepherd ◽  
Plasma Pharmacokinetics ◽  
Healthy Dogs ◽  
Over 40 Years

Diminazene remains one of South Africa's most commonly used antiprotozoal agents for the management of babesiosis in dogs . Although the drug has been on the market for over 40 years, its intravenous pharmacokinetics are poorly known. To better understand the pharmacokinetics of the drug Berenil®, it was reconstituted in sterile water and administered intravenously to 6 adult German shepherd dogs. All 6 dogs demonstrated the previously described secondary peak in the plasma concentration versus time profile. The plasma pharmacokinetics for diminazene are described by both non-compartmental and compartmental models. From non-compartmental analysis, the area under curve to the last sample point (AUClast), clearance (CL) and volume of distribution (Vz) were 4.65±1.95 ng/mℓ/h, 0.77±0.18 ℓ/kg/h and 2.28±0.60 ℓ/kg, respectively. For compartmental modelling, the plasma concentrations were fitted to both a 2-compartmental open model and a recirculatory enterohepatic model. From the recirculation model, the rate of release and re-entry into the central compartment varied markedly with the rate of release from the gall bladder (Ttom) being estimated at 27 ± 20.90 h. Once released, drug re-entry into the central compartment was variable at 9.70±5.48 h. With normal biliary excretion time being about 2 h, this indicates that the redistribution cannot be occurring physiologically from the bile. Although it was not possible to identify the site from which sequestration and delayed release is occurring, it is believed that it is most likely from the liver. The study therefore showed that the secondary peak described for the pharmacokinetics of intramuscular administered diminazene in the dog is not related to biphasic absorption.

The effect of a ketamine constant rate infusion on cardiovascular variables in sheep anesthetized at the minimum alveolar concentration of sevoflurane that blunts adrenergic responses

2022 ◽  
pp. 1-7
Author(s):  
Kevin Chang ◽  
Michele Barletta ◽  
Kristen M. Messenger ◽  
Daniel M. Sakai ◽  
Rachel A. Reed ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Minimum Alveolar Concentration ◽  
Plasma Concentrations ◽  
Face Mask ◽  
Constant Rate Infusion ◽  
Carbon Dioxide Rebreathing ◽  
Constant Rate ◽  
Significant Difference ◽  
Treatment Administration ◽  
Rate Infusion

Abstract OBJECTIVE To evaluate the effect of a constant rate infusion of ketamine on cardiac index (CI) in sheep, as estimated using noninvasive cardiac output (NICO) monitoring by partial carbon dioxide rebreathing, when anesthetized with sevoflurane at the previously determined minimum alveolar concentration that blunts adrenergic responses (MACBAR). ANIMALS 12 healthy Dorset-crossbred adult sheep. PROCEDURES Sheep were anesthetized 2 times in a balanced placebo-controlled crossover design. Anesthesia was induced with sevoflurane delivered via a tight-fitting face mask and maintained at MACBAR. Following induction, sheep received either ketamine (1.5 mg/kg IV, followed by a constant rate infusion of 1.5 mg/kg/h) or an equivalent volume of saline (0.9% NaCl) solution (placebo). After an 8-day washout period, each sheep received the alternate treatment. NICO measurements were performed in triplicate 20 minutes after treatment administration and were converted to CI. Blood samples were collected prior to the start of NICO measurements for analysis of ketamine plasma concentrations. The paired t test was used to compare CI values between groups and the ketamine plasma concentrations with those achieved during the previous study. RESULTS Mean ± SD CI of the ketamine and placebo treatments were 2.69 ± 0.65 and 2.57 ± 0.53 L/min/m2, respectively. No significant difference was found between the 2 treatments. Mean ketamine plasma concentration achieved prior to the NICO measurement was 1.37 ± 0.58 µg/mL, with no significant difference observed between the current and prior study. CLINICAL RELEVANCE Ketamine, at the dose administered, did not significantly increase the CI in sheep when determined by partial carbon dioxide rebreathing.

Pharmacokinetics and organ metabolism of carboxyamidated and glycine-extended gastrins in pigs

1996 ◽  
Vol 271 (1) ◽  
pp. G156-G163 ◽  
Author(s):  
C. P. Hansen ◽  
F. Stadil ◽  
L. Yucun ◽  
J. F. Rehfeld
Keyword(s):  
Clearance Rate ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Constant Rate Infusion ◽  
Constant Rate ◽  
Vascular Beds ◽  
Apparent Volume Of Distribution ◽  
Rate Infusion

The elimination of carboxyamidated gastrin-17 and its glycine-extended precursor was studied in anesthetized pigs during constant-rate infusion. Extraction of amidated gastrin-17 was recorded in the hindlimb (42%), kidney (40%), head (32%, P < 0.001), and the gut (13%, P < 0.01). Elimination was not recorded in the liver, lungs, or heart. Extraction of glycine-extended gastrin-17 was measured in the kidney (36%), hindlimb (31%, P < 0.001), head (26%), and the gut (16%, P < 0.01), but not in the liver or the lungs. Glycine-extended gastrin-17 was not processed to amidated gastrin during infusion. The half-life, metabolic clearance rate, and apparent volume of distribution for amidated gastrin-17 were 3.5 +/- 0.4 min, 15.5 +/- 1.1 ml.kg-1.min-1, and 76.5 +/- 9.9 ml/kg, respectively, and for glycine-extended gastrin-17 were 4.3 +/- 0.6 min, 17.4 +/- 0.9 ml.kg-1.min-1, and 104.7 +/- 11.9 ml/kg, respectively. We conclude that extraction of amidated and glycine-extended gastrin-17 varies in the vascular beds, with elimination mainly confined to nonorgan tissues and the kidneys.

Effects of a constant rate infusion of magnesium sulphate in healthy dogs anaesthetized with isoflurane and undergoing ovariohysterectomy

2012 ◽  
Vol 39 (6) ◽  
pp. 599-610 ◽  
Author(s):  
Eva Rioja ◽  
Brighton T Dzikiti ◽  
Geoffrey Fosgate ◽  
Amelia Goddard ◽  
Frik G Stegmann ◽  
...  
Keyword(s):  
Magnesium Sulphate ◽  
Constant Rate Infusion ◽  
Constant Rate ◽  
Healthy Dogs ◽  
Rate Infusion

scholarly journals The Effects of Prophylactic Dexmedetomidine Administration on General Anesthesia Recovery Quality in Healthy Dogs Anesthetized With Sevoflurane and a Fentanyl Constant Rate Infusion Undergoing Elective Orthopedic Procedures

2021 ◽  
Vol 8 ◽  
Author(s):  
Sarah K. Jarosinski ◽  
Bradley T. Simon ◽  
Courtney L. Baetge ◽  
Stephen Parry ◽  
Joaquin Araos
Keyword(s):  
Rating Scale ◽  
Numerical Rating Scale ◽  
Orthopedic Procedures ◽  
Bolus Administration ◽  
Treatment Groups ◽  
Locoregional Anesthesia ◽  
Numerical Rating ◽  
Healthy Dogs ◽  
End Tidal ◽  
Rate Infusion

To determine the effects of a dexmedetomidine slow bolus, administered prior to extubation, on recovery from sevoflurane-anesthesia and a fentanyl continuous rate infusion (CRI) in dogs undergoing orthopedic surgical procedures. Sixty-two client-owned, healthy dogs weighing 27.4 ± 11 kg undergoing elective orthopedic procedures were premedicated with: 0.1 mg/kg hydromorphone intramuscular, 0.05 mg/kg hydromorphone intravenously (IV) or 5 mcg/kg fentanyl IV. Following premedication, dogs were induced with propofol, administered locoregional anesthesia and maintained with sevoflurane and a fentanyl CRI (5–10 mcg/kg/hr). Dogs were randomly assigned to one of two treatment groups: 0.5 mcg/kg dexmedetomidine (DEX) or 0.5 ml/kg saline (SAL). Following surgery, patients were discontinued from the fentanyl CRI and administered DEX or SAL IV over 10 min. Following treatment, dogs were discontinued from sevoflurane and allowed to recover without interference. Recoveries were video recorded for 5 min following extubation and assessed by two blinded anesthesiologists using a visual analog scale (VAS; 0–10 cm) and a numerical rating scale (NRS; 1–10). Mean arterial pressure (MAP), heart rate (HR), pulse oximetry (SpO2), temperature, respiratory rate (RR), and end-tidal sevoflurane (EtSevo) and carbon dioxide (EtCO2) concentrations were recorded at specific time-points from induction to 5 min post-bolus administration and analyzed using linear mixed models. Fentanyl, propofol, and hydromorphone dose and the time to extubation were compared using an unpaired t-test. Differences in recovery scores between groups were evaluated with a Mann-Whitney test. Data reported as mean ± SD or median [interquartile range] when appropriate. A p &lt; 0.05 was significant. There were no significant differences between groups in fentanyl, propofol, and hydromorphone dose, duration of anesthesia, intraoperative MAP, HR, RR, SpO2, temperature, EtCO2, EtSevo or anesthetic protocol. MAP was higher in DEX compared to SAL at 10 (104 ± 27 and 83 ± 23, respectively) and 15 (108 ± 28 and 86 ± 22, respectively) min after treatment. DEX had significantly lower VAS [0.88 (1.13)] and NRS [2.0 (1.5)] scores when compared to SAL [VAS = 1.56 (2.59); NRS = 2.5 (3.5)]. Time to extubation (min) was longer for DEX (19.7 ± 11) when compared to SAL (13.4 ± 10). Prophylactic dexmedetomidine improves recovery quality during the extubation period, but prolongs its duration, in sevoflurane-anesthetized healthy dogs administered fentanyl.

Sufentanil pharmacokinetics in a full-term neonate treated with extracorporeal membrane oxygenation: a case report

Perfusion ◽  
2019 ◽  
Vol 34 (5) ◽  
pp. 433-436 ◽  
Author(s):  
Pavla Pokorná ◽  
Martin Šíma ◽  
Václav Vobruba ◽  
Martina Bašková ◽  
Lenka Posch ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Case Report ◽  
Extracorporeal Membrane Oxygenation ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Data ◽  
Analgesic Drug ◽  
Membrane Oxygenation ◽  
Ischemic Encephalopathy

Introduction: Sufentanil is a potent analgesic drug used for pain management. A few studies describe the pharmacokinetics of sufentanil in neonates; however, no pharmacokinetic data about sufentanil during extracorporeal membrane oxygenation have been published yet. Case report: A 1-day-old neonate with moderate hypoxic–ischemic encephalopathy received veno-arterial extracorporeal membrane oxygenation support for refractory respiratory and circulatory failure. Sufentanil plasma concentrations were determined during both extracorporeal membrane oxygenation (n = 14) and non–extracorporeal membrane oxygenation (n = 17) period. Based on these measurements, individual sufentanil pharmacokinetic parameters were calculated. Discussion: We observed increased sufentanil volume of distribution (11.6 vs 5.6 L/kg) and decreased sufentanil clearance (0.535 vs 0.746 L/h/kg) in extracorporeal membrane oxygenation period. The increment of volume of distribution was attributed to ECMO influence, while difference in clearance was probably due to drug interaction. Conclusions: This is the first description of sufentanil pharmacokinetics in neonate treated with extracorporeal membrane oxygenation. We observed considerably larger volume of distribution during extracorporeal membrane oxygenation period in comparison with non–extracorporeal membrane oxygenation period.

scholarly journals Pharmacokinetic Properties of Single-Dose Primaquine in Papua New Guinean Children: Feasibility of Abbreviated High-Dose Regimens for Radical Cure of Vivax Malaria

2013 ◽  
Vol 58 (1) ◽  
pp. 432-439 ◽  
Author(s):  
Brioni R. Moore ◽  
Sam Salman ◽  
John Benjamin ◽  
Madhu Page-Sharp ◽  
Leanne J. Robinson ◽  
...  
Keyword(s):  
Single Dose ◽  
Vivax Malaria ◽  
Venous Blood ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
Population Pharmacokinetic ◽  
High Dose ◽  
Pharmacokinetic Data ◽  
Radical Cure ◽  
Papua New Guinean

ABSTRACTSince conventional 14-day primaquine (PMQ) radical cure of vivax malaria is associated with poor compliance, and as total dose, not therapy duration, determines efficacy, a preliminary pharmacokinetic study of two doses (0.5 and 1.0 mg/kg of body weight) was conducted in 28 healthy glucose-6-phosphate dehydrogenase-normal Papua New Guinean children, aged 5 to 12 years, to facilitate development of abbreviated high-dose regimens. Dosing was with food and was directly observed, and venous blood samples were drawn during a 168-h postdose period. Detailed safety monitoring was performed for hepatorenal function and hemoglobin and methemoglobin concentrations. Plasma concentrations of PMQ and its metabolite carboxyprimaquine (CPMQ) were determined by liquid chromatography-mass spectrometry and analyzed using population pharmacokinetic methods. The derived models were used in simulations. Both single-dose regimens were well tolerated with no changes in safety parameters. The mean PMQ central volume of distribution and clearance relative to bioavailability (200 liters/70 kg and 24.6 liters/h/70 kg) were within published ranges for adults. The median predicted maximal concentrations (Cmax) for both PMQ and CPMQ after the last dose of a 1.0 mg/kg 7-day PMQ regimen were approximately double those at the end of 14 days of 0.5 mg/kg daily, while a regimen of 1.0 mg/kg twice daily resulted in a 2.38 and 3.33 times higherCmaxfor PMQ and CPMQ, respectively. All predicted medianCmaxconcentrations were within ranges for adult high-dose studies that also showed acceptable safety and tolerability. The present pharmacokinetic data, the first for PMQ in children, show that further studies of abbreviated high-dose regimens are feasible in this age group.

scholarly journals Cardiorespiratory, Sedative and Antinociceptive Effects of a Medetomidine Constant Rate Infusion with Morphine, Ketamine or Both

Animals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 2081
Author(s):  
Lucas Troya-Portillo ◽  
Javier López-Sanromán ◽  
María Villalba-Orero ◽  
Isabel Santiago-Llorente
Keyword(s):  
Healthy Adult ◽  
Constant Rate Infusion ◽  
Treatment Groups ◽  
Constant Rate ◽  
Antinociceptive Effects ◽  
Negative Effect ◽  
Rate Infusion ◽  
Related Mortality ◽  
All Treatment

Standing surgery under sedation reduces anesthetic-related mortality in horses. Medetomidine, alone and combined with morphine in a constant rate infusion (CRI), has been described for standing surgery but their cardiorespiratory, sedative and antinociceptive effects have never been compared. The addition of ketamine could improve analgesia in these procedures with minimal cardiorespiratory consequences. The objectives were to compare the cardiorespiratory effects, quality of sedation, antinociception and ataxia produced by administration of a medetomidine-based CRI with morphine, ketamine or both, in standing horses. A prospective, blind, randomized crossover, experimental design with six healthy adult horses was performed, in which four treatments were administered to all horses with at least two weeks of washout period: medetomidine (M); medetomidine and ketamine (MK); medetomidine and morphine (MMo); and medetomidine, morphine and ketamine (MMoK). Dosages were the same in all treatment groups: medetomidine at 5 µg/kg bwt followed by 5 µg/kg bwt/h, ketamine at 0.4 mg/kg/h and morphine at 50 µg/kg bwt, followed by morphine 30 µg/kg bwt/h. Drug infusions were maintained for 120 min. Cardiorespiratory variables, sedation degree and antinociceptive effects were evaluated during the procedure. All combinations produced similar sedation and antinociceptive effects and no clinically relevant alterations in cardiorespiratory variables occurred. Medetomidine CRI combined with morphine, ketamine or both are suitable and safe protocols for standing sedation in horses and the addition of morphine and/or ketamine did not cause any negative effect but no improving effect on sedation and antinociception was detected.

Diurnal Rhythm in Anticoagulant Effect of Heparin during a Low Dose Constant Rate Infusion

1992 ◽  
Vol 68 (01) ◽  
pp. 030-032 ◽  
Author(s):  
J W M Krulder ◽  
A de Boer ◽  
A M H P van den Besselaar ◽  
A F Cohen ◽  
H C Schoemaker ◽  
...  
Keyword(s):  
Control Experiment ◽  
Plasma Concentrations ◽  
Anticoagulant Effect ◽  
Diurnal Rhythms ◽  
Clotting Time ◽  
Platelet Factor ◽  
Constant Rate ◽  
Coagulation Tests ◽  
Rate Infusion

SummaryThe objective of the study was to investigate possible diurnal rhythms in coagulation tests during a continuous intravenous infusion of unfractionated heparin. Six volunteers participated in the study, which was divided in a treatment (500 U heparin/h for 30 h) and a control experiment. Under basal conditions, no rhythm was found in coagulation tests. During heparin treatment, APTT, thrombin clotting time and anti-Xa activity showed a greater anticoagulant effect at night, with a striking decrease in the morning.In a search for the explanation of this phenomenon we looked for diurnal variations in the urinary excretion of heparin, in the plasma concentrations of antithrombin III and platelet factor 4, and in the effect of heparin added to the plasma samples in vitro. None of these studies provided the explanation.

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