scholarly journals Physiological and Clinical Responses in Pigs in Relation to Plasma Concentrations during Anesthesia with Dexmedetomidine, Tiletamine, Zolazepam, and Butorphanol

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1482
Author(s):  
Anneli Rydén ◽  
Marianne Jensen-Waern ◽  
Görel Nyman ◽  
Lena Olsén
Keyword(s):  
Intramuscular Injection ◽  
Plasma Concentrations ◽  
Spontaneous Respiration ◽  
Pharmacokinetic Parameters ◽  
Repeated Injection ◽  
Clinical Effects ◽  
Short Term ◽  
Drug Plasma Concentrations ◽  
Drug Plasma ◽  
Clinical Responses

Reliable protocols for short-term anesthetics are essential to safeguard animal welfare during medical investigations. The aim of the study was to assess the adequacy and reliability of an anesthetic protocol and to evaluate physiological and clinical responses, in relation to the drug plasma concentrations, for pigs undergoing short-term anesthesia. A second aim was to see whether an intravenous dosage could prolong the anesthesia. The anesthesia was induced by an intramuscular injection of dexmedetomidine, tiletamine zolazepam, and butorphanol in 12 pigs. In six of the pigs, a repeated injection intravenously of one-third of the initial dose was given after one hour. The physiological and clinical effects from induction to recovery were examined. Plasma concentrations of the drugs were analyzed and pharmacokinetic parameters were calculated. Each drug’s absorption and time to maximal concentration were rapid. All pigs were able to maintain spontaneous respiration. The route of administration did not alter the half-life of the drug. The results suggest that intramuscular administration of the four-drug combination provides up to two hours of anesthesia with stable physiological parameters and an acceptable level of analgesia while maintaining spontaneous respiration. A repeated intravenous injection may be used to extend the time of anesthesia by 30 min.

Antiarrhythmic Drug Plasma Concentrations in Ambulatory Patients

1996 ◽  
Vol 30 (3) ◽  
pp. 298-300 ◽  
Author(s):  
Roberto Latini ◽  
Gianna Magnolfi ◽  
Rossella Zordan ◽  
Mariano Ferrari ◽  
Roberto Padrini ◽  
...  
Keyword(s):  
Antiarrhythmic Drug ◽  
Plasma Concentrations ◽  
Drug Plasma Concentrations ◽  
Drug Plasma ◽  
Ambulatory Patients

Concentration-response relationships for three nonsteroidal anti-inflammatory drugs in the rat intestine

1995 ◽  
Vol 14 (7) ◽  
pp. 573-579 ◽  
Author(s):  
J. Ford ◽  
JB Houston
Keyword(s):  
Rank Order ◽  
Plasma Concentrations ◽  
Intestinal Damage ◽  
Rat Intestine ◽  
Response Data ◽  
Drug Plasma Concentrations ◽  
Drug Plasma ◽  
Constant Rate ◽  
Inflammatory Drugs ◽  
Intestinal Permeation

1. The effect of diclofenac, piroxicam and (S+)-ibuprofen upon the rat intestine has been measured at constant drug plasma concentrations in the rat, using (51Cr)-EDTA intestinal permeation as a measure of damage. Initially disposition studies after sc administration of the three NSAIDs were carried out. From these studies it was found that constant-rate iv infusions were necessary to maintain plasma concentrations of diclofenac and (S+)-ibuprofen. Administration of piroxicam by sc bolus gave relatively constant plasma concentrations, thus iv infusions were not necessary to obtain concentration-response data for this drug. Relative potency was found by comparing the con centration-response profiles of the three NSAIDs and the rank order of potency obtained was: diclofenac > piroxi cam > (S+)-ibuprofen. 2. The effect of mode of administration upon intestinal damage was also investigated using diclofenac. Intestinal permeability was measured in rats given diclofenac either by sc bolus or iv infusion and dose-response data com pared. It was found that for the same dose, administration by sc bolus gave a higher degree of damage than by iv infusion.

scholarly journals Clinical Pharmacology Aspects of Some Tocolytic Drugs Used in Pregnant Women at Risk of Preterm Birth

2019 ◽  
Vol 9 (3) ◽  
pp. 162-166
Author(s):  
E. A. Sоkоvа ◽  
R. A. Chilova ◽  
O. A. Demidova ◽  
K. O. Akopov
Keyword(s):  
Preterm Birth ◽  
Pregnant Women ◽  
Preterm Labour ◽  
Plasma Concentrations ◽  
Cyclooxygenase Inhibitors ◽  
Pharmacokinetic Parameters ◽  
Clinical Effects ◽  
Spontaneous Preterm Birth ◽  
Rational Pharmacotherapy ◽  
The Impact

Spontaneous preterm birth is one of the most pressing issues in obstetrics, as it remains one of the leading causes of newborn morbidity and mortality. Pending issues of aetiology, pathogenesis, and absence of medicinal products indicated for the treatment of spontaneous preterm labour pose a challenge for rational pharmacotherapy. The paper presents the results of a scientific literature review on the problem of rational pharmacotherapy of spontaneous preterm labour using tocolytic drugs — calcium channel blockers, cyclooxygenase inhibitors. The paper summarises specific pharmacokinetic parameters of these drugs during pregnancy. It discusses pharmacogenetic aspects of using tocolytic drugs in pregnant women and their potential clinical effects. It was demonstrated that women with threatened miscarriage had high interindividual variability in nifedipine plasma concentrations depending on CYP3A5 genotype. It was shown that certain genetic polymorphisms of CYP2C9 may lead to an increased metabolic rate and an increase in indomethacin clearance resulting in the reduction of its efficacy. Yet, there is minimal research regarding this issue. Therefore, further research is needed to assess the impact of CYP3A5 and CYP2C9 genotypes on the efficacy and safety of nifedipine and indomethacin used as tocolytic drugs in obstetrics.

Relationship Between Antiretroviral Drug Plasma Concentrations and Viral Load in Children

2003 ◽  
Vol 32 (1) ◽  
pp. 112-115 ◽  
Author(s):  
J. M. Treluyer ◽  
M. Burgard ◽  
N. Cazali ◽  
P. Quartier ◽  
F. Veber ◽  
...  
Keyword(s):  
Viral Load ◽  
Plasma Concentrations ◽  
Drug Plasma Concentrations ◽  
Drug Plasma ◽  
Antiretroviral Drug

Clinical pharmacodynamics of continuous infusion teniposide: systemic exposure as a determinant of response in a phase I trial.

1987 ◽  
Vol 5 (7) ◽  
pp. 1007-1014 ◽  
Author(s):  
J H Rodman ◽  
M Abromowitch ◽  
J A Sinkule ◽  
F A Hayes ◽  
G K Rivera ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Plasma Concentrations ◽  
Systemic Exposure ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Variability ◽  
Significant Relationships ◽  
Clinical Responses ◽  
The Mean ◽  
Dose Levels ◽  
Severe Mucositis

Teniposide (VM-26) is an effective anticancer drug usually administered as a short infusion in doses of 150 to 165 mg/m2. The objectives of the trial reported here were to evaluate clinical responses and assess pharmacokinetic parameters as a determinant of outcome when VM-26 was administered as a 72-hour continuous infusion (CI) with doses escalated from 300 to 750 mg/m2 per course. Twenty-eight patients with recurrent leukemia, lymphoma, or neuroblastoma received 53 courses of CI VM-26 and 16 had measurable responses. There were two partial remissions and one stable disease among seven neuroblastoma patients and 13 of 21 leukemia/lymphoma patients had oncolytic responses (greater than or equal to 75% decrease in circulating blasts). Toxicity included moderate to severe mucositis and myelosuppression. Pharmacokinetic parameters determined during 35 courses administered to 23 patients were highly variable. Clearance (CI) ranged between 3.7 and 43.8 ml/min/m2, resulting in VM-26 plasma concentrations from 2.8 to 30.6 mg/L across all dose levels. The interpatient pharmacokinetic variability reflected in CI and VM-26 steady state concentrations (Css), obscured any dose-response relationship. However, when pharmacokinetic parameters for responding and nonresponding patients were compared, statistically significant relationships were observed. For responders, the mean Css was 15.2 mg/L and mean CI was 12.1 mL/min/m2; for nonresponders, mean Css was 6.2 mg/L (P less than .01) and mean CI was 21.3 mL/min/m2 (P less than .05). Thus, patients with higher CI and lower Css were less likely to respond. Clinical responses occurred in ten of ten patients with Css greater than 12 mg/L, and only five of 13 patients with Css less than 12 mg/L (P less than .01). In this study, interpatient pharmacokinetic variability yielded a four- to sixfold difference in intensity of systemic exposure (Css) within the same dose level, which was an important determinant of clinical response. These data indicate that achieving a VM-26 target concentration for individual patients could ensure an increased intensity of systemic exposure in patients with a high CI and improve the likelihood of effective therapy.

scholarly journals Neural correlates of the DMT experience assessed with multivariate EEG

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Christopher Timmermann ◽  
Leor Roseman ◽  
Michael Schartner ◽  
Raphael Milliere ◽  
Luke T. J. Williams ◽  
...  
Keyword(s):  
Subjective Experience ◽  
Brain Activity ◽  
Plasma Concentrations ◽  
Oscillatory Activity ◽  
Visual Component ◽  
Eyes Closed ◽  
Drug Plasma Concentrations ◽  
Drug Plasma ◽  
Oscillatory Power ◽  
Signal Diversity

AbstractStudying transitions in and out of the altered state of consciousness caused by intravenous (IV) N,N-Dimethyltryptamine (DMT - a fast-acting tryptamine psychedelic) offers a safe and powerful means of advancing knowledge on the neurobiology of conscious states. Here we sought to investigate the effects of IV DMT on the power spectrum and signal diversity of human brain activity (6 female, 7 male) recorded via multivariate EEG, and plot relationships between subjective experience, brain activity and drug plasma concentrations across time. Compared with placebo, DMT markedly reduced oscillatory power in the alpha and beta bands and robustly increased spontaneous signal diversity. Time-referenced and neurophenomenological analyses revealed close relationships between changes in various aspects of subjective experience and changes in brain activity. Importantly, the emergence of oscillatory activity within the delta and theta frequency bands was found to correlate with the peak of the experience - particularly its eyes-closed visual component. These findings highlight marked changes in oscillatory activity and signal diversity with DMT that parallel broad and specific components of the subjective experience, thus advancing our understanding of the neurobiological underpinnings of immersive states of consciousness.

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