Pharmacokinetic interactions half-life

As mentioned earlier, pharmacokinetics is not solely the property of a drug but instead is the consequence of interactions between the drug and the physiology of the patient. Thus, statements like the half-life of gentamicin is 2 hours are not very useful, as the half-life is likely be longer or shorter in a given individual patient. 

Mechanism of Action An alcohol abuse deterrent that appears to interact with glutamate and gamma-aminobutyric acid neurotransmitter systems centrally, restoring their balance. Therapeutic Effect Reduces alcohol dependence. Pharmacokinetics Slowly absorbed from the G1 tract. Steady-state plasma concentrations are reached within 5 days. Does not undergo metabolism. Excreted in urine. Half-life 20-33 hr. 

Mechanism of Action Aprotein that binds to tumor necrosis factor (TNF), blocking its interaction with cell surface receptors. Elevated levels of TNF, which is involved in inflammatory and immune responses, are found in the synovial fluid of rheumatoid arthritis patients. Therapeutic Effect Relieves symptoms of rheumatoid arthritis. Pharmacokinetics Well absorbed after subcutaneous administration. Half-life 115 hr. 

SSRI of choice based on intermediate half-life, linear pharmacokinetics, absence of appreciable age effect on clearance, substantially less effect on P450 enzymes, reducing potential for drug interactions... 

Maximal plasma concentrations occur 2 to 3 hours after oral administration of reboxetine (178). Reboxetine has linear pharmacokinetics over its clinically relevant dosing range and a half-life of approximately 12 hours. For this latter reason, a twice a day, equally divided dosing schedule was used during clinical trial development. Its clearance is reduced and half-life becomes longer as a function of advanced age (mean = 81 years of age) and renal and hepatic impairment ( 178, 322, 323). Reboxetine is principally metabolized by CYP 3A3/4 such that its dose should be reduced when used in combination with drugs that are substantial inhibitors of CYP (e.g., certain azole antifungals, certain macrolide antibiotics). Reboxetine itself, however, does not cause detectable inhibition of CYP 3A3/4 based on formal in vivo pharmacokinetic interaction studies as well as its own linear pharmacokinetics. 

Sotalol is well absorbed orally with bioavailability of approximately 100%. It is not metabolized in the liver and is not bound to plasma proteins. Excretion is predominantly by the kidneys in the unchanged form with a half-life of approximately 12 hours. Because of its relatively simple pharmacokinetics, solatol exhibits few direct drug interactions. Its most significant cardiac adverse effect is an extension of its pharmacologic action a dose-related incidence of torsade de pointes that approaches 6% at the highest recommended daily dose. Patients with overt heart failure may experience further depression of left ventricular function during treatment with sotalol. 

In another study by the same investigators, 10 healthy volunteers were randomized in a two-way, crossover study either to oral lovastatin or to intravenous diltiazem followed by oral lovastatin. Intravenous diltiazem did not significantly affect the pharmacokinetics of lovastatin (oral AUC, Cmax, tmax, or half-life), suggesting that the interaction does not occur systemically and is primarily a first-pass effect (11). Drug interactions with diltiazem may therefore become evident when a patient is changed from intravenous to oral dosing. 

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