Preg-M Mechanism of Action

Pharmacology: Pharmacokinetics: Pregabalin: Absorption: Pregabalin is rapidly absorbed when administered in the fasted state, with peak plasma concentrations occurring within 1 hour following both single and multiple dose administration. Pregabalin oral bioavailability is estimated to be ≥90% and is independent of dose. Following repeated administration, steady-state is achieved within 24 to 48 hours. The rate of Pregabalin absorption is decreased when given with 24 to 48 hours. The rate of Pregabalin absorption is decreased when given with food resulting in a decrease in Cmax by approximately 25%-30% and a delay in tmax to approximately 2.5 hours. However, administration of pregabalin with food has no clinically significant effect on the extent of pregabalin absorption.
Distribution: In preclinical studies, pregabalin has been shown to cross the blood brain barrier in mice, rats, and monkeys. Pregabalin has been shown to cross the placenta in rats and is present in the milk of lactating rats. In humans, the apparent volume of distribution of pregabalin following oral administration is approximately 0.56 L/kg. Pregabalin is not bound to plasma proteins.
Metabolism: Pregabalin undergoes negligible metabolism in humans. Following a dose of radiolabelled pregabalin, approximately 98% of the radioactivity recovered in the urine was unchanged pregabalin. The N-methylated derivative of pregabalin, the major metabolite of pregabalin found in urine, accounted for 0.9% of the dose. In preclinical studies, there was no indication of racemization of pregabalin S-enantiomer to the R-enantiomer.
Elimination: Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug.
Pregabalin mean elimination half-life is 6.3 hours. Pregabalin plasma clearance and renal clearance are directly proportional to creatinine clearance.
Dosage adjustment in patients with reduced renal function or undergoing hemodialysis is necessary.
Linearity/non-linearity: Pregabalin pharmacokinetics are linear over the recommended daily dose range. Inter-subject pharmacokinetic variability for pregabalin is low (<20%). Multiple dose pharmacokinetics are predictable from single-dose date. Therefore, there is no need for routine monitoring of plasma concentrations of pregabalin.
Mecobalamin: Substances bind to intrinsic factor; a glycoprotein, secreted by the gastric mucosa and are then actively absorbed from the gastrointestinal tract. Absorption is impaired in patients with an absence of intrinsic factor, with a malabsorption syndrome or with disease or abnormality of the gut, or after gastrectomy. Absorption from the gastrointestinal tract can also occur by passive diffusion; little of the vitamin present in food absorbed in this manner although the process becomes increasingly important with larger amounts such as those used therapeutically. After intranasal dosage, peak plasma concentrations of cyanocobalamin have been reached in 1 to 2 hours. The bioavailability preparation is about 7 to 11% of that by intramuscular injection.
Vitamin B₁₂ is extensively bound to specific plasma proteins called transcobalamins; transcobalamin II appears to be involved in the rapid transport of the cobalamins into tissues. Vitamin B₁₂ is stored in the liver, excreted in the bile, and undergoes extensive enterohepatic recycling; part of however, accounts for only a small fraction in the reduction of total body stores acquired by dietary means. Vitamin B₁₂ diffuses across the placenta and also appears in breast milk.