Unique Pharmacokinetic and Pharmacodynamic Parameters of Antimicrobials in Goats

Abstract

Pharmacokinetics, the process that involves drug absorption, distribution, metabolism and excretion (ADME) of antimicrobials, determines pharmacodynamic response, that is, what drugs do to the body. Therefore, of all the pharmacokinetic parameters, elimination half-life (T 1 / 2 β), volume of distribution (Vd), maximum plasma concentration (Cmax) and maximum time reached (Tmax) are the most important parameters. Hence, the parameters are unique in determining pharmacokinetic and pharmacodynamic response of antimicrobials. However, it is elimination half-life and minimum inhibitory concentration (MIC) that determine the dosing interval of antimicrobials. The dose range of 2.5 mg/kg for gentamicin passing through 4 mg/kg (ciprofloxacin), 4.2 mg/kg (ampicillin L/A), 5 mg/kg (kanamycin, enrofloxacin, gatifloxacin and norfloxacin), 7 mg/kg (mequindox), 10 mg/kg (amikacin, enrofloxacin, lincomycin, pefloxacin, cefpirome, erythromycin and isoniazid), 20 mg/kg (oxytetracycline) and 30 mg/kg (metronidazole) have elimination half-life of 1.2-67.2 h, Cmax of 0.12-54.4 μg/ml, Tmax of 0.2-24 h, bioavailability of 16-99.8% and plasma protein binding of 0->80% when administered intramuscularly, intravenously and orally. Human equivalent dose formula could be used to extrapolate human-goat therapeutic doses of antimicrobials. However, some antimicrobials such as sulfadimidine, tulathromycin, oxytetracycline and azithromycin may have high residues in the milk, kidneys, liver, intestines, brain and skeletal muscles and may portend high risk of antimicrobial resistance, hypersensitivity reaction, epidermal necrolysis, Stevens-Johnson syndrome and other adverse drug reactions.

The effects of extended feeding of florfenicol coated medicated diets on the safety, serum biomarkers and blood cells morphology of Nile tilapia Oreochromis niloticus (L.)

“…Cytotoxicity was prominent in the 5X and 10X groups with distinguishably irregular RBCs, ruptured cells and eccentric nuclei. Cytotoxicity of FFC at the higher concentrations has been well demonstrated in goats and reptiles (Saganuwan 2019). Nevertheless, the therapeutic dose did not show any signs of cell rupture hinting at the safety of FFC at the test dose.…”

Application of Modified Michaelis – Menten Equations for Determination of Enzyme Inducing and Inhibiting Drugs

“…Elimination half-life, volume of distribution which is responsible for drug transport to sites of metabolism, maximum plasma concentration which could determine metabolism enzyme saturation and maximum time reached (Tmax) may be used to determine time of enzyme saturation, pharmacokinetic and pharmacodynamic response of drugs (Saganuwan, 2019). Cell organelles involved in metabolism and their dimensions are adiposomes (20nm-I ) amphisomes (822 ± 37nm) apicoplast (0.15 -1.5…”

Application of modified Michaelis – Menten equations for determination of enzyme inducing and inhibiting drugs

“…Elimination half-life, volume of distribution which is responsible for drug transport to sites of metabolism, maximum plasma concentration which could determine metabolism, enzyme saturation and elimination and maximum time (Tmax) reached, may be used to determine time of enzyme saturation, pharmacokinetic and pharmacodynamic response of drugs [ 1 ]. Cell organelles involved in metabolism and their dimensions are adiposomes (20 nm–I μm ), amphisomes (822 ± 37 nm), apicoplast (0.15–1.5 μm ), autophagosome (0.15–1.5 μm ), chloroplast (2–10 μm ), enlargesome, enosome (30–100 nm), lysosome (0.1–1.2 nm), melanosome (≃ 500 nm), mitochondria (0.5–5 μm ), nucleus (≃ 10 μm ), peroxisome (500 nm), phagosome (0.9–3 μm ), secretory granule (820 ± 16 μm ) and secretory synaptosome (0.5–3 μm ).…”