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Oral Drug Administration (oral + drug_administration)

Distribution by Scientific Domains

Medical Sciences	50%

Selected Abstracts

A convenient method for estimating the quantity of drug eliminated by the routes other than hepatic metabolism and renal excretion and the fraction of drug that reaches the "first pass" after oral administration

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2006
Leonid M. Berezhkovskiy
Abstract The comparison of routine pharmacokinetic data obtained after intravenous and oral drug administration allows to figure out that some quantity of drug, which reached the systemic circulation, was eliminated from the body by routes other than hepatic metabolism and renal excretion. This quantity is equal or exceeds the certain minimum value, which can be calculated from a simple equation obtained in the article. If the minimum value is equal to zero, then the maximum possible fraction of orally administered drug, that is, absorbed into the gut wall and gets through it unchanged, can be calculated. The examples considered indicate that the quantity of drug eliminated not by liver metabolism or kidney excretion could be quite substantial (exceeds half of the dose that reached the circulation). © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:828,833, 2006 [source]

The influence of drug kinetics in blood on the calculation of oral bioavailability in linear pharmacokinetics: The traditional equation may considerably overestimate the true value,

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2006
Leonid M. Berezhkovskiy
Abstract A common calculation of oral bioavailability is based on the comparison of the areas under the concentration-time curves after intravenous and oral drug administration. It does not take into account that after the oral dosing a drug enters the systemic circulation in different states, that is, as free fraction, protein bound and partitioned into blood cells, and plasma lipids, while after intravenous input it is introduced into the systemic circulation only as a free fraction. Consideration of this difference leads to a novel equation for the oral bioavailability. In general, the traditional calculation overestimates the oral bioavailability. For a widely applied model of a linear pharmacokinetic system with central (plasma) drug elimination it is shown that the traditional calculation of the oral bioavailability could substantially overestimate the true value. If the existence of an immediate equilibrium between different drug fractions in blood is assumed, the obtained equation becomes identical to the traditional one. Thus the deviation of oral bioavailability from the value given by a common calculation appears to be a kinetic phenomenon. The difference could be significant for the drugs with the rate constant of elimination from plasma of the same order of magnitude or greater than the dissociation rate constant of drug,protein complexes, or the off-rate constant of partitioning from the blood cells, if the blood concentration profiles were used to calculate the oral bioavailability. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:834,848, 2006 [source]

Stereoselective pharmacokinetic analysis of tramadol and its main phase I metabolites in healthy subjects after intravenous and oral administration of racemic tramadol

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 1 2007
Emilio García Quetglas
Abstract The kinetics of tramadol enantiomers are stereoselective when doses of the racemic drug are given orally. To document whether the route of administration determines the stereoselective kinetics of tramadol enantiomers, healthy volunteers received 100 mg oral or intravenous doses of racemic tramadol, and serial blood samples were obtained to assay tramadol enantiomers and their main phase I metabolites, O -demethyltramadol and N -demethyltramadol. To assess accurately the involvement of their metabolites in the pharmacokinetics of tramadol, it is essential to determine the rate and extent of the formation of the enantiomers of these metabolites. A simultaneous pharmacokinetic model describing the plasma concentration-curves of the generated metabolites and the parent compounds after intravenous and oral drug administration is developed and presented. Tramadol and O -demethyltramadol were the major compounds detected in plasma after intravenous administration. Nevertheless, the N -demethylation of tramadol showed a significant increase when the oral route was used. After both oral and intravenous doses, the kinetics of the tramadol enantiomers were stereoselective. The AUC for (R )-(+)-tramadol was greater than the AUC for (S)-(,)-tramadol. The formation of N -demethyltramadol also was enantioselective after oral administration of racemic tramadol, with a greater AUC for (R)-(+)- N -demethyltramadol than for (S)-(,)- N -demethyltramadol. In the opposite form, (S)-(,)- O -demethyltramadol was formed faster than (R)-(+)- O -demethyltramadol. The metabolism of tramadol was also route-dependent with a different enantiomeric ratio for tramadol and its main phase I metabolites after intravenous and oral administration. The disposition of N -demethyltramadol was concentration-dependent. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Intravesical alkalinized lidocaine (PSD597) offers sustained relief from symptoms of interstitial cystitis and painful bladder syndrome

BJU INTERNATIONAL, Issue 7 2009
J. Curtis Nickel
OBJECTIVE To assess the immediate and sustained relief of the symptoms of interstitial cystitis/painful bladder syndrome (IC/PBlS) after a consecutive 5-day course of treatment with intravesical alkalinized lidocaine (PSD597), and to characterize the pharmacokinetics of single and multiple doses of intravesical PSD597 in a subgroup of patients. PATIENTS AND METHODS In all, 102 adult patients (99 women) with a clinical diagnosis of IC/PBlS were randomized from 19 centres in the USA and Canada to receive a daily intravesical instillation of PSD597 (200 mg lidocaine, alkalinized with a sequential instillation of 8.4% sodium bicarbonate solution, to a final volume of 10 mL) or placebo (double-blind), for 5 consecutive days. Patients were followed at intervals up to 29 days after the first instillation. Efficacy was assessed by changes in the Global Response Assessment (GRA), Likert scales for bladder pain, urgency and frequency, and validated O'Leary-Sant IC symptom and problem indices. RESULTS Significantly more patients treated with PSD597 rated their overall bladder symptoms as moderately or markedly improved on the GRA scale 3 days after completing the 5-day course of treatment (30% and 9.6%, respectively, for patients treated with PSD597 and placebo; P = 0.012). The treatment effects were also maintained beyond the end of treatment and are further supported by the secondary endpoints, including symptom and problem indices. The peak serum lidocaine concentration during the study was <2 µg/mL, and well below the toxic level (>5 µg/mL). CONCLUSION This preliminary study showed that PSD597 was effective for providing sustained amelioration of symptoms of IC/PBlS beyond the acute treatment phase. The drug was safe, well tolerated and devoid of the systemic side-effects often experienced with oral drug administration. Long-term studies are needed to determine the optimum regimen to maintain this favourable treatment effect. [source]