Experimental Neurology By Prof Paul Glees Pp xii + 532 (Oxford: Clarendon Press; London: Oxford University Press, 1961) 75s net

The Nervous System

Growth and development can be investigated using readily observable demographic factors such as weight and age. Size is the primary covariate and can be referenced to a 70-kg person with allometry using a coefficient of 0.75 for clearance and 1 for volume. The use of these coefficients is supported by fractal geometric concepts and observations from diverse areas in biology. Fat free mass (FFM) might be expected to do better than total body weight when there are wide variations in fat affecting body composition. Clearance pathways develop in the fetus before birth. The use of postnatal age as a descriptor of maturation is unsatisfactory because birth may occur prematurely; therefore postmenstrual age is a superior predictor of elimination function. A sigmoid E(max) model (Hill equation) describes gradual maturation of clearance in early life leading to a mature adult clearance achieved at a later age.

Mechanism-Based Concepts of Size and Maturity in Pharmacokinetics

The maturation of organ systems during fetal life and childhood exerts a profound effect on drug disposition. The maturation of drug-metabolising enzymes is probably the predominant factor accounting for age-associated changes in non-renal drug clearance. The group of drug-metabolising enzymes most studied are the cytochrome P450 (CYP) superfamily. The CYP3A subfamily is the most abundant group of CYP enzymes in the liver and consists of at least 3 isoforms: CYP3A4, 3A5 and 3A7. Many drugs are mainly metabolised by the CYP3A subfamily. Therefore, maturational changes in CYP3A ontogeny may impact on the clinical pharmacokinetics of these drugs. CYP3A4 is the most abundantly expressed CYP and accounts for approximately 30 to 40% of the total CYP content in human adult liver and small intestine. CYP3A5 is 83% homologous to CYP3A4, is expressed at a much lower level than CYP3A4 in the liver, but is the main CYP3A isoform in the kidney. CYP3A7 is the major CYP isoform detected in human embryonic, fetal and newborn liver, but is also detected in adult liver, although at a much lower level than CYP3A4. Substrate specificity for the individual isoforms has not been fully elucidated. Because of large interindividual differences in CYP3A4 and 3A5 expression and activity, genetic polymorphisms have been suggested. However, although some gene mutations have been identified, the impact of these mutations on the pharmacokinetics of CYP3A substrates has to be established. Ontogeny of CYP3A activity has been studied in vitro and in vivo. CYP3A7 activity is high during embryonic and fetal life and decreases rapidly during the first week of life. Conversely, CYP3A4 is very low before birth but increases rapidly thereafter, reaching 50% of adult levels between 6 and 12 months of age. During infancy, CYP3A4 activity appears to be slightly higher than that of adults. Large interindividual variations in CYP3A5 expression and activity were observed during all stages of development, but no apparent developmental pattern of CYP3A5 activity has been identified to date. Profound changes occur in the activity of CYP3A isoforms during all stages of development. These changes have, in many instances, proven to be of clinical significance when treatment involves drugs that are substrates, inhibitors or inducers of CYP3A. Investigators and clinicians should consider the impact of ontogeny on CYP3A in both pharmacokinetic study design and data interpretation, as well as when prescribing drugs to children.

Cytochrome P450 3A: ontogeny and drug disposition.

Section I: The Normal Bird: Systematics. Reproductive Physiology. Nutrition. Laws and Regulations Affecting Aviculture and the Pet Bird Industry. Embryology. Pediatricsand Hand Raising. Behavior. Avicultural Medicine and Flock Health Management. Nonsurgical Methods of Avian Sex Identification. Section II: Diagnostics, Hospital Techniques, And Supportive Care: Physical Examination. Avian Clinical Pathology: Hematologyand Chemistry. Diagnostic Necropsy and Pathology. Radiology. Ultrasonography. Cytology. Differential Diagnostics. Hospital Techniques and Supportive Care. Section III: Infectious Diseases: Bacteriology. Virology. Mycotic Diseases. Parasitology. Zoonotic Diseases. Chlamydia. Mycoplasmal Infections. Section IV: Noninfectious Diseases: Respiratory Disorders. Gastrointestinal Tract. Avian Nervous System. The Endocrine System. Avian Cardiac Disease. Nutritional Disorders. Disorders of the Musculoskeletal System. Avian Dermatology. Disorders of the Special Senses. Neoplasia. Toxicities. Urogenital Disorders. Diseases of the Avian Immune System. Behavioral Problems. Section V: Pharmacology and Therapeutics: Metabolism, Pharmacology, And Therapy. Formulary.

鳥類の内科学と外科学 : Avian medicine and surgery

Analysis of anticancer drugs: a review.

Effects of intravenous lidocaine, ketamine, and the combination on the minimum alveolar concentration of sevoflurane in dogs.

Effect of intravenous lidocaine and ketamine on the minimum alveolar concentration of isoflurane in goats

Objective—To determine the pharmacokinetics of an orally administered dose of tramadol in domestic rabbits (Oryctolagus cuniculus). Animals—6 healthy adult sexually intact female New Zealand White rabbits. Procedures—Physical examinations and plasma biochemical analyses were performed to ensure rabbits were healthy prior to the experiment. Rabbits were anesthetized with isoflurane, and IV catheters were placed in a medial saphenous or jugular vein for collection of blood samples. One blood sample was collected before treatment with tramadol. Rabbits were allowed to recover from anesthesia a minimum of 1 hour before treatment. Then, tramadol (11 mg/kg, PO) was administered once, and blood samples were collected at various time points up to 360 minutes after administration. Blood samples were analyzed with high-performance liquid chromatography to determine plasma concentrations of tramadol and its major metabolite (O-desmethyltramadol). Results—No adverse effects were detected after oral administration of ...

Pharmacokinetics of orally administered tramadol in domestic rabbits (Oryctolagus cuniculus).

Analgesia is becoming increasingly important in veterinary medicine, and little research has been performed that examined pain control in avian species. Tramadol is a relatively new drug that provides analgesia by opioid (m), serotonin, and norepinephrine pathways, with minimal adverse effects. To determine the pharmacokinetics of tramadol and its major metabolite O-desmethyltramadol (M1) in eagles, 6 bald eagles (Haliaeetus leucocephalus) were each dosed with tramadol administered intravenously (4 mg/kg) and orally (11 mg/kg) in a crossover study. Blood was collected at various time points between 0 and 600 minutes and then analyzed with high-performance liquid chromatography to determine levels of tramadol and M1, the predominate active metabolite. The terminal half-life of tramadol after intravenous dosing was 2.46 hours. The maximum plasma concentration, time of maximum plasma concentration, and terminal half-life for tramadol after oral dosing were 2156.7 ng/ml, 3.75 hours, and 3.14 hours, respectively. In addition, the oral bioavailability was 97.9%. Although plasma concentrations of tramadol and M1 associated with analgesia in any avian species is unknown, based on the obtained data and known therapeutic levels in humans, a dosage of 5 mg/kg PO q12h is recommended for bald eagles. Pharmacodynamic studies are needed to better determine plasma levels of tramadol and M1 associated with analgesia in birds.

https://bioone.org/journals/journal-of-avian-medicine-and-surgery/volume-23/issue-4/1082-6742-23.4.247/Pharmacokinetics-of-Intravenous-and-Oral-Tramadol-in-the-Bald-Eagle/10.1647/1082-6742-23.4.247.pdf

Sherry K. Cox

Papers

Effects of intravenous lidocaine, ketamine, and the combination on the minimum alveolar concentration of sevoflurane in dogs.

Effect of intravenous lidocaine and ketamine on the minimum alveolar concentration of isoflurane in goats

Pharmacokinetics of orally administered tramadol in domestic rabbits (Oryctolagus cuniculus).

Pharmacokinetics of Intravenous and Oral Tramadol in the Bald Eagle (Haliaeetus leucocephalus)

Effects of tramadol on the minimum alveolar concentration of sevoflurane in dogs