Activity pharmacokinetics

HCV-796 is a non-nucleosidic NS5B polymerase inhibitor with potent antiviral activity in vitro. A phase lb study was performed to determine the antiviral activity, pharmacokinetics, and safety of HCV-796 in patients with chronic HCV infection. Maximum antiviral effects were achieved after 4 days of treatment with a mean reduction of HCV-RNA of 1.4 loglOIU/ml. Combination of HCV-796 with pegylated interferon-a led to a greater reduction of viral RNA load (3.3-3.5 loglO lU/ml) after a 14 days treatment interval. 

A review discussing anthelmintic activity, pharmacokinetics, toxicity, side effects, and clinical use of niclosamide and other anthelmintic agents is reported [95],... 

Brogden RN, Peters DH Teicoplanin A reappraisal of its antimicrobial activity, pharmacokinetic properties and therapeutic efficacy. Drugs 1994 47 823-854. 

Gillis JC, Brogden RN Rifaximin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic potential in conditions mediated by gastrointestinal bacteria. Drugs 1995 49 467-484. 

Mechanism of Action A betaj-adrenergic blocker that competitively blocks beta,-adrenergic receptors in cardiac tissue. Reduces the rate of spontaneous firing of the sinus pacemaker and delays AV conduction. Therapeutic Effect Slows heart rate, decreases cardiac output, decreases BP, and exhibits antiarrhythmic activity. Pharmacokinetics ... 

Mechanism of Action Clioquinol is a broad-spectrum antibacterial agent but the mechanism of action is unknown. Hydrocortisone is a corticosteroid that diffuses across cell membranes, forms complexes with specific receptors and further binds to DNA and stimulates transcription of mRNA (messenger RNA) and subsequent protein synthesis of various enzymes thought to be ultimately responsible for the anti-inflammatory effects of corticosteroids applied topically to the skin Therapeutic Effect Alters membrane function and produces antibacterial activity Pharmacokinetics Clioquinol may be absorbed through the skin in sufficient amounts. 

Mecfianism of Action An anticonvulsant that inhibits burst firing without affecting normal neuronal excitability. Therapeutic Effect Prevents seizure activity. Pharmacokinetics Rapidly and almost completely absorbed through the GI tract. Protein binding less than 10%. Insignificant amount metabolized in liver. Excreted in urine. Removed by hemodialysis. Half-life 7 hr. 

Mechanism of Action A tetracyclic compound that blocks reuptake norepi nephri ne by CNS presynaptic neuronal membranes, increasing availability at postsynaptic neuronal receptor sites, and enhances synaptic activity. Therapeutic Effect Produces antidepressant effect, with prominent sedative effects and low anticholinergic activity. Pharmacokinetics Slowly and completely absorbed after PO administration. Protein binding 88%. Metabolized in liver by hydroxylation and oxidative modification. Excreted in urine. Unknown if removed by hemodialysis. Half-life 27-58 hr. 

Mechanism of Action An antibiotic that alters cell membrane permeability in susceptible microorganisms. Therapeutic Effect Bactericidal activity Pharmacokinetics Negligible absorption. Protein binding low. Excreted in urine. Poor removal in hemodialysis. Half-life 6 hr. 

K. R. Beutner (1995). Valacyclovir A review of its antiviral activity, pharmacokinetics and clinical efficacy. Antiviral Res. 28 281. 

Mattison LK, Fourie J, Hirao Y et al. The uracil breath test in the assessment of dihydropyrimidine dehydrogenase activity pharmacokinetic relationship between expired 13C02 and plasma [2-13C]dihydrouracil. Clin Cancer Pes 2006 12 549-555. 

Perry CM, Faulds D. 1997. Lamivudine A review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy in the management of HIV infection. Drugs. 53 657-680. 

R.N. Brogden, and R.C. Heel, Human insulins A review of its biological activity, pharmacokinetic and therapeutic use. Drugs 34 350-371, 1987. 

Robertson DW, Katzenellenbogen JA, Long DJ, Rorke EA, Katzenellenbogen BS (1982) Tamoxifen antiestrogens - a comparison of the activity, pharmacokinetics, and metabolic-activation of the cis-isomer and trans-isomer of tamoxifen. J Steroid Biochem 16 1-13... 

Scavone ]M, Gleckman RA, Fraser DG. Cinoxacin mechanism of action, spectrum of activity, pharmacokinetics, adverse reactions, and therapeutic indications. Pharmacotherapy, 1982, 2, 266-272. 

Quantitative structure-activity/pharmacokinetic relationships (QSAR/ QSPKR) for a series of synthesized DHPs and pyridines as Pgp (type I (100) II (101)) inhibitors was generated by 3D molecular modelling using SYBYL and KowWin programs. A multivariate statistical technique, partial least square (PLS) regression, was applied to derive a QSAR model for Pgp inhibition and QSPKR models. Cross-validation using the leave-one-out method was performed to evaluate the predictive performance of models. For Pgp reversal, the model obtained by PLS could account for most of the variation in Pgp inhibition (R2 = 0.76) with fair predictive performance (Q2 = 0.62). Nine structurally related 1,4-DHPs drugs were used for QSPKR analysis. The models could explain the majority of the variation in clearance (R2 = 0.90), and cross-validation confirmed the prediction ability (Q2 = 0.69) [ 129]. 

Potency/biological activity Pharmacokinetic profile Absorption time from tissue vs. IV Circulating half-life Distribution and elimination kinetics Toxicological profile Immunogenic potential Patient population characteristics Disease state Pathophysiology Age... 

Goa KL, McTavish D, Clissold SP. Ivermectin. A review of its antifilarial activity, pharmacokinetic properties and clinical efficacy in onchocerciasis. Drugs 1991 42 640-658. 

Wagstaff AJ, Bryson HM (1994) Foscarnet A reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic use in immunocompromised patients with viral infections. Drugs 48 153-205. 

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