Drug metabolism, pharmacokinetic administration routes

As mentioned above, bioavailability is the degree to which a drug reaches the intended site of action. The amount of drug that reaches systemic circulation will depend on the processes of absorption, distribution, and biotransformation (when the route of administration exposes the drug to first-pass metabolism). Pharmacokinetics are often linear and when they are nonlinear it is often due to a saturation of protein binding, metabolism, or active renal transport. 

Pharmacokinetics Administration can be by an intravenous, oral, or topical route. The efficacy of topical applications is doubtful. The drug distributes well throughout the body, including the cerebrospinal fluid. Acyclovir is partially metabolized to an inactive product. Excretion into the urine occurs both by glomerular filtration and tubular secretion. Acyclovir accumulates in patients with renal failure. 

Drug metabolism and pharmacokinetics, which normally include bio-analytical chemistry, to assess the delivery and disposition profile of the leads in animal models using the route of administration projected for clinical studies... 

Drug Metabolic Products - Pharmacokinetics Cephalothin was partially converted to deacetylcephalothin after parenteral administration to experimental animals and to man.23 in the dog, initial excretion was distributed equally between cephalothin and its deacetyl metabolite later excretion showed a preponderance of the metabolite over the parent compound. Cephalothin persisted over a longer period of time when administered by the intramuscular route than when given intravenously. In man, the total amount excreted in the urine was... 

In terms of pharmacokinetics, many host factors, such as the route of administration, the metabolism, the catabolism and clearance will considerably determine the anti neoplastic success of a drug. One major difficulty with the clinical effectiveness of chemotherapy of neoplastic diseases is the requirement that it kill malignant tumor cells at doses that allow cells in the patient s vital organs to survive so that the recovery can occur. In other words, it is to obtain a reasonably safe therapeutic index favoring introduction into clinical practice. 

Thus, %F is defined as the area under the curve normalized for administered dose. Blood drug concentration is affected by the dynamics of dissolution, solubility, absorption, metabolism, distribution, and elimination. In addition to %F, other pharmacokinetic parameters are derived from the drug concentration versus time plots. These include the terms to describe the compound s absorption, distribution, metabolism and excretion, but they are dependent to some degree on the route of administration of the drug. For instance, if the drug is administered by the intravenous route it will undergo rapid distribution into the tissues, including those tissues that are responsible for its elimination. 

Borlak J, Blickwede M, Hansen T, Koch W, Walles M, Levsen K (2005) Metabolism of verapamil in cultures of rat alveolar epithelial cells and pharmacokinetics after administration by intravenous and inhalation routes. Drug Metab Dispos 33(8) 1108-1114... 

Pharmacokinetics Phenylephrine is irregularly absorbed from and readily metabolized in the GI tract. After IV administration, a pressor effect occurs almost immediately and persists for 15-20 minutes. After IM administration, a pressor effect occurs within 10-15 minutes and persists for 50 minutes to 1 hour. After oral inhalation of phenylephrine in combination with isoproterenol, pulmonary effects occur within a few minutes and persist for about 3 hours. The pharmacologic effects of phenylephrine are terminated at least partially bythe uptake of the drug into the tissues. Phenylephrine is metabolized in the liver and intestine by the enzyme monoamine oxidase (MAO). The metabolites and their route and rate of excretion have not been identified. 

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