General Pharmacology

• The comparison of the bioavailability of two dosage forms is called bioequivalence.

The bioequivalence of different preparations is assessed by an evaluation of three parameters: (1) the peak height concentration achieved by the drug in the dosage form, (2) the time to reach the peak concentration of the drug, and (3) the area under the concentration-time curve. The ascending limb of the curve is considered to be a general reflection of the rate of drug absorption from the dosage form. The descending limb of the concentration-time curve is a general indication of the rate of elimination of the drug from the body.

• PLASMA PROTEIN BINDING:

Because only the free (unbound) fraction of a drug can cross biologic membranes, binding to plasma proteins limits a drug's concentration in tissues and, therefore, decreases the apparent Vd of the drug. Plasma protein binding will also reduce glomerular filtration of the drug because this process is highly dependent on the free drug fraction. Renal tubular secretion and biotransformation of drugs are generally not limited by plasma protein binding because these processes reduce the free drug concentration in the plasma. If a drug is avidly transported through the tubule by the secretion process or is rapidly biotransformed, the rates of these processes may exceed the rate of dissociation of the drug-protein complex (in order to restore the free:bound drug ratio in plasma) and, thus, become the rate-limiting factor for drug elimination. This assumes that equilibrium conditions exist and that other influences (e.g., changes in pH or the presence of other drugs) do not occur.

• t1/2 = 0.7 × Vd/CL

• Loading dose = Vd x Cp/F

Maintenance dose = CL x Cp/F

• Cl_organ = Q × ER

ER = (C_A ×C_V)/ CA

Sodium Channel Toxins :Tetrodotoxin and Saxitoxin, Ciguatoxin and Batrachotoxin

• For a 70-kg individual, total body water is about 40 L (0.6 L/kg); interstitial plus plasma water occupies about 12 L (0.17 L/kg).
• Dispositional antagonism is a term sometimes used to describe the ability of one drug to enhance the elimination (and so reduce the serum levels and intensity of responses to) of another drug. Thus, it is mainly a pharmacokinetic interaction. Its most common basis involves one drug enhancing the metabolic inactivation and elimination of another drug. For example, phenytoin (anticonvulsant/antiepileptic drug) or rifampin induce the hepatic metabolic inactivation of warfarin, reducing (antagonizing) warfarin’s anticoagulant activity by reducing its serum levels.

• Grapefruit juice (but not most other citrus juices) contains compounds (e.g., naringin, furanocoumarins) that can inhibit the metabolism of several drugs, one of which is cyclosporine, specifically via inhibitory effects on CYP3A4. The effect is especially important for hepatic metabolism of oral drugs that are susceptible to the first-pass effect and on CYP3A4. (Other drugs involved in this interaction include verapamil, some of the statin type cholesterol-lowering medications; most of the second generation antihistamines, including fexofenadine; and several antidepressants and antihypertensives.) The result is increased bioavailability of an orally administered dose and increased AUC. Peak and total (integrated over time) plasma levels of the interactant typically are increased, and one potential (if not likely) outcome is excessive (toxic) effects.

• There are four major components to this mixed-function oxidase system: (1) cytochrome P450, (2) NADPH, or reduced nicotinamide adenine dinucleotide phosphate, (3) NADPH–cytochrome P450 reductase, and (4) molecular oxygen.