Excretion drug distribution

DIFFUSION OF LIGAND TO RECEPTOR Drug clearance, dosage, PHARMACOKINETICS Drug distribution kinetics, PHARMACOKINETICS Drug excretion rates,... 

Pregnancy Increased blood volume Increased renal blood flow and GFR Reduced plasma albumin Increased hepatic metabolism Altered drug distribution between protein bound and free forms Greater excretion of renally-cleared drugs May need increased dose to maintain effective Cp... 

B. Clearance is defined as the volume of fluid from which drug is completely removed per unit of time and as such is a measure of the body s abihty to remove drug by whatever manner (e.g., ehmination, metabolism, excretion). Distribution is the theoretical volume to which the drug distributes and metabolism and excretion are simply methods of clearing drug. 

The initial unequal tissue-drug distribution cannot persist, however, because physicochemical forces tend to require an eventual establishment of concentration equilibria with other less well perfused organs. Therefore, as the drug continues to be removed from the blood by the less richly perfused tissues or eliminated by metabolism and excretion or both, plasma levels will fall, and the concentration of anesthetic in the brain will decline precipitously. 

Teicoplanin, like vancomycin, is not absorbed from the intestinal tract. Peak plasma levels are achieved about 2 hours after intramuscular administration. The drug distributes widely in tissues plasma protein binding is about 90%. The half-Ufe approximates 50 hours, which is considerably longer than that of vancomycin, and may make it useful for outpatient administration. Like vancomycin, teicoplanin is excreted by the kidneys. 

Factors analogous to those affecting gut absorption also can affect drug distribution and excretion. Any transporters or metabolizing enzymes can be taxed to capacity—which clearly would make the kinetic process nonlinear (see Linear versus Nonlinear Pharmacokinetics ). In order to have linear pharmacokinetics, all components (distribution, metabolism, filtration, active secretion, and active reabsorption) must be reasonably approximated by first-order kinetics for the valid design of controlled release delivery systems. 

Absorption of a drug into the theoretical central or main compartment may be followed by distribution into one or more peripheral compartments, or the drug may undergo excretion or metabolism from the central compartment. While compartmental analysis of drug distribution can be informative, it is beyond the scope of this book. For more details on the effect of multicompartmental distribution of a drug on pharmacokinetics, see references in the Bibliography. 

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. 

The GC/MS procedures for methamphetamine are described in Table 4. The papers published in Japanese - have corresponding reports in English. - - Methamphetamine was detected and determined by mass fragmentography in rat hair after administration of the substance. Nine methods also detected the metabolite amphetamine or amphetamine alone. Suzuki et al. determined methamphetamine also in nail, sweat and saliva. The workup (EX after acid or alkaline hydrolysis) and derivatization technique (methanol-trifluoroacetic acid [TEA]) is rather uniform in most procedures. Nakahara et al. ° used methoxyphenamine excretion into beard hair to discuss several washing procedures. Alkaline or methanolic extraction are used with one exception. Derivatization is mainly made by fluorinated anhydrides. A review ° gives details on analytical procedures, incorporation rates of amphetamines from blood to hair, and relationship between drug history and drug distribution in hair. 

Reed, M.D. The ontogeny of drug disposition Focus on drug absorption, distribution, and excretion. Drug Inform. J. 1996, 30, 1129-1134. 

Once they enter the body, drugs are absorbed into the blood and distributed to their site(s) of action. The body also works to metabolize and excrete drugs that enter it. 

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... 

P-glycoprotein (P-gp, Table 8.2) plays an important role in determining drug distribution of many important drug candidates. P-gp substrates generally have reduced oral drug absorption and enhanced renal and biliary excretion. Limiting the exposure of xenobiotics to P-gp at the blood-brain barrier and placenta] barrier may also be important considerations. The rapid identification of P-gp substrates or... 

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