Evaluation of Alternative Oseltamivir (Tamiflu) Dosing Strategies.

Launched by US DEPARTMENT OF VETERANS AFFAIRS · Mar 16, 2006

Keywords

ClinConnect Summary

In vitro studies have determined that the 50 % inhibitory concentrations (IC50) of Ro 64-0802 against influenza neuraminidases ranged from 0.3 to 22 nmol/L (0.08 - 0.28 g/L or 0.08 -0.28 ng/mL). IC50 values against influenza strains in cell culture were somewhat higher and more variable ranging from 0.6 to 155 nmol/L (0.17 - 32.8 g/L or 0.17 - 32.8 ng/mL). Tamiflu has also been shown to have in vitro and mouse challenge activity against the H5N1 virus. EC50 values against H5N1 strain replication in Madin Darby canine kidney (MDCK) cells ranged from 7.5-12 M and neuraminidase activity from 7...

Gender

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Eligibility criteria

• Inclusion Criteria:
• • Subjects will include males and non-pregnant females 18 years or older Subjects who can understand the study and potential safety concerns and can sign the informed consent form prior to admission to this study Subjects that are willing to complete all the required assessments, tests and evaluations and able to make all study visits Hemoglobin \> 10.0 g/dL for males and \> 9.0 g/dL for females; b) Platelet count of \> 75,000 / L; c) Absolute neutrophil count \> 1000 / L; SGOT and SGPT \< than 2.5 times normal upper limit (UL); Serum uric acid WNL; Creatinine \< 1.5 times normal upper limit (normal UL 1.5 mg/dL) for the \< 65 years of age group and MUST be WNL for the \> 65 years of age group; creatinine clearance \> 50 mL/min
• Exclusion Criteria:
• • Subjects with a creatinine clearance of \< 50 mL/min Subjects who are pregnant or breast feeding females Subjects who are not employing adequate contraception Subjects who are drug or alcohol abusers and in the opinion of the investigator would interfere with subject compliance and safety Subjects who are currently participating in any other clinical research study Any acute serious infection requiring prescription therapy within 14 days prior to Day 1 of the study Subjects who may have or recently been exposed to influenza Subjects with gout, blood dyscrasias, or history of hypersensitivity to sulfonamide drugs Subjects with contraindications to the study medications History of allergic reaction to probenecid Have kidney disease, kidney stones, or poorly functioning kidneys Have active peptic ulcer disease On high dose aspirin or salicylate therapy
• Receiving any of the following medications (relative contraindication for probenecid):
• • Acyclovir, allopurinol, penicillamine, clofibrate, rifampin, methotrexate, zidovudine, theophylline, dapsone, penicillins or cephalosporins, nonsteroidal anti-inflammatory drugs (NSAIDS) such as ibuprofen (Motrin, Advil, Nuprin, others), ketoprofen (Orudis, Oruvail, Orudis KT), diclofenac (Cataflam, Voltaren), etodolac (Lodine), fenoprofen (Nalfon), flurbiprofen (Ansaid), indomethacin (Indocin), ketorolac (Toradol), nabumetone (Relafen), oxaprozin (Daypro), piroxicam (Feldene), sulindac (Clinoril), tolmetin (Tolectin), and naproxen (Aleve, Anaprox, Naprosyn); a sulfa-based medication such as sulfamethoxazole (Bactrim, Septra, Gantanol), sulfasalazine (Azulfidine), sulfinpyrazone (Anturane), sulfisoxazole (Gantrisin), and others; an oral diabetes medicine such as glipizide (Glucotrol), glyburide (Micronase, Diabeta, Glynase), tolbutamide (Orinase), or tolazamide (Tolinase); a barbiturate such as phenobarbital (Luminal, Solfoton), amobarbital (Amytal), secobarbital (Seconal), and others; or a benzodiazepine (used to treat anxiety and panic disorders and to induce sleep) such as alprazolam (Xanax), diazepam (Valium), lorazepam (Ativan), temazepam (Restoril), chlordiazepoxide (Librium), clonazepam (Klonopin), clorazepate (Tranxene), oxazepam (Serax), estazolam (ProSom), flurazepam (Dalmane), quazepam (Doral), or triazolam (Halcion).