Topical administration pharmacokinetics

Often the demand for such a complement of properties requires a hierarchical strategy in which only the broadest possible limits are satisfied by the less demanding design requirements. For example, topical administration assists in limiting toxicity while improving targeting and pharmacokinetic response. On the other hand, the requirements for effective... 

Pharmacokinetics The disposition of lodoxamide was studied in 6 healthy adult volunteers receiving a 3 mg oral dose. Urinary excretion was the major route of elimination. The elimination half-life was 8.5 hours in urine. In a study in 12 healthy adult volunteers, topical administration of 1 drop in each eye 4 times/day for 10 days did not result in any measurable lodoxamide plasma levels at a detection limit of 2.5 ng/mL. 

Pharmacokinetics Topical administration appears to produce effective concentrations within the corneal stroma, but not in intraocular fluid. Absorption from the Gl tract is very poor. Systemic absorption should not occur after topical administration. 

Pharmacokinetics Poorly absorbed by topical administration. Well absorbed from mucous membranes and traumatized skin. Metabolized in liver and by hydrolysis with cholinesterase. Minimal excretion in urine. 

Pharmacokinetics Minimal absorption after topical administration. Minimal excretion in urine and feces. 

Pharmacokinetics Well absorbed from GI tract following PO administration. Protein binding 9I%-99%. Metabolized in liver. Primarily excreted in bile with minimal elimination in urine. Negligible systemic absorption following topical absorption. Ketoconazole is not detected in plasma after shampooing or topical administration. Half-... 

Pharmacokinetics Absorbed through devascularized areas into systemic circulation following topical administration. Efxcreted in the form of its metabolite rho-carboxy-benzenesulfonamide... 

Pharmacokinetics Measurable penciclovir concentrations were not detected in plasma or urine. The systemic absorption of penciclovir following topical administration has not been evaluated. 

Selectivity of action is based on several factors. Some drugs stimulate either muscarinic receptors or nicotinic receptors selectively. Some agents stimulate nicotinic receptors at neuromuscular junctions preferentially and have less effect on nicotinic receptors in ganglia. Organ selectivity can also be achieved by using appropriate routes of administration ("pharmacokinetic selectivity"). For example, muscarinic stimulants can be administered topically to the surface of the eye to modify ocular function while minimizing systemic effects. 

The pharmacokinetics and ocular bioavailability of topical NSAIDs in the horse are unknown. In other species, topical NSAIDs readily penetrate and disseminate within the eye, reaching peak intraocular levels within 2 h. In general, the levels achieved by topical administration exceed those... 

Pharmacokinetic Well absorbed after PO, sublingual, topical administration. Undergoes extensive first-pass metabolism in liver excreted in urine not removed by dialysis... 

For all routes of administration, the absorption, distribution, and elimination kinetics are important for obtaining the desired therapeutic effect. For drugs expected to act in the eye after ocular absorption, pharmacokinetic parameters are difficult to obtain in both animals and humans. Accordingly, it has been proposed to rely essentially on pharmacodynamic measurements by use of a specific biological response after topical administration (258,259). For example, the apparent absorp-... 

Mechanisms and pharmacokinetics Cidofovir is activated exclusively by host cell kinases and inhibits DNA polymerases of HSV, CMV, adenovirus, and papillomavirus. Resistance is due to mutations in the DNA pol5merase gene. The drug has been used by intravenous and topical administration and by intravitreal injection. Cidofovir undergoes renal elimination in proportion to creatinine clearance. 

Babbar S, Marier JF, Bley K. Pharmacokinetic analysis of capsaicin after topical administration of a high-concentration capsaicin patch to patients with peripheral neuropathic pain. NeurogesX inc, San Mateo, California 94404, USA. 

The time pattern of drug absorption and disposition in the eye following topical administration is a complex phenomenon, influenced by the drug, the vehicle, and by anatomical/physiological factors. In order to understand the pharmacokinetics of ocular drugs it is necessaiy to consider the absorption, distribution and disposition of drugs in three areas of the eye (a) the preocular (precorneal) area, (b) the cornea, and (c) the interior of the eye. A picture of the pathways for absorption, and of their complex interrelations is given in Fig. 2. 

Sjoquist, B. Tajallaei, S. Stjernschantz, J. Pharmacokinetics of latanoprost in the cynomolgus monkey. 1st communication single intravenous, oral or topical administration on the eye, Arzneimittelforschung, 1999, 49, 225-233. 

The separation of enantiomers is a very important topic to the pharmaceutical industry. It is well recognized that the biological activities and bioavailabilities of enantiomers often differ [1]. To further complicate matters, the pharmacokinetic profile of the racemate is often not just the sum of the profiles of the individual enantiomers. In many cases, one enantiomer has the desired pharmacological activity, whereas the other enantiomer may be responsible for undesirable side-effects. What often gets lost however is the fact that, in some cases, one enantiomer may be inert and, in many cases, both enantiomers may have therapeutic value, though not for the same disease state. It is also possible for one enantiomer to mediate the harmful effects of the other enantiomer. For instance, in the case of indacrinone, one enantiomer is a diuretic but causes uric acid retention, whereas the other enantiomer causes uric acid elimination. Thus, administration of a mixture of enantiomers, although not necessarily racemic, may have therapeutic value. 

Cellai L, Colosimo M, Marchi E, Venturini AP, Zanolo G Rifaximin (L/105), a new topical intestinal antibiotic Pharmacokinetic study after single oral administration of 3H-rifaximin to rats. Chemioterapia (Florence) 1984 3 373-377. 

Detailed pharmacokinetic investigations are a necessary prelude to the formal approval protocols of the Federal Drug Administration and its counterparts worldwide. Although this topic lies beyond the scope of this Hand-... 

Pharmacokinetics Not significantly absorbed following topical or ophthalmic administration. 

Pharmacokinetics Rapidly and almost completely absorbed following PO administration. After topical application, limited absorption systemically. Metabolized in liver. Excreted in urine. Half-life 36-54 hr. 

Some pharmacokinetic properties of the commonly used amide local anesthetics are summarized in Table 26-2. The pharmacokinetics of the ester-based local anesthetics have not been extensively studied owing to their rapid breakdown in plasma (elimination half-life < 1 minute). Local anesthetics are usually administered by injection into dermis and soft tissues around nerves. Thus, absorption and distribution are not as important in controlling the onset of effect as in determining the rate of offset of local analgesia and the likelihood of CNS and cardiac toxicity. Topical application of local anesthetics (eg, transmucosal or transdermal) requires drug diffusion for both onset and offset of anesthetic effect. However, intracavitary (eg, intra-articular, intraperitoneal) administration is associated with a more rapid onset and shorter duration of local anesthetic effect. 

Various characteristics of the molecule influence its chances of reaching its target receptor since they influence the nature and extent of the body s effect on it. A drug s pharmacokinetic profile therefore determines the extent of the drug s opportunity to exert its pharmacodynamic effect. While there are various routes for human drug administration (oral rectal intravenous, subcutaneous, intramuscular, and intra-arterial injections topical and direct inhalation into the lungs), the most common for small-molecule drugs is oral administration, and discussions in the first part of this chapter therefore focus on oral administration. (In contrast, biopharmaceuticals are typically administered by injection, often directly into the bloodstream.)... 

As was noted in Chapter 4, pharmacokinetic and pharmacodynamic effects are studied in nonclinical research. These topics are also of critical importance in clinical investigations. A drug s pharmacokinetics and pharmacodynamics are of considerable interest to clinicians who may prescribe the drug to patients once it is approved. Meaningful decisions about a drug s optimal use can only be made with an understanding of the time course of events that occur after the drug s administration, and both pharmacokinetics and pharmacodynamics are concerned with this time course. By consideration of the pharmacokinetic processes of absorption, distribution, metabolism, and excretion (ADME), the... 

Pharmacokinetics Epinephrine has a rapid onset but brief duration of action. In emergency situations epinephrine is given intravenously for the most rapid onset of action it may also be given subcutaneously, by endotracheal tube, by inhalation, or topically to the eye. Oral administration is ineffective, since epinephrine and the other catecholamines are inactivated by intestinal enzymes. Only metabolites are excreted in the urine. 

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