Efficacy equivalence

Compared to streptokinase, urokinase has been less extensively studied because of its high cost, ie, about 10 times that of a comparable treatment with streptokinase. In addition to the indications described for streptokinase, urokinase is indicated for use in patients with prior streptokinase treatment, or prior Streptococcal infection. Urokinase is commonly used at a loading dose of 4400 units /kg, with a maintenance intravenous infusion dose of 4400 units/kg/h for thromboses other than acute myocardial infarction. In the latter case, a much larger dose, ie, 0.5—2.0 million units/h or a bolus dose of 1.0 million units followed by a 60-min infusion with 1.0 million units, has been found optimal (106). An intracoronary dose of 2000 units/min for two hours was used in one comparative study with intracoronary streptokinase (107). In this study, urokinase exhibited efficacy equivalent to streptokinase with fewer side effects. Other studies with intracoronary urokinase have adrninistered doses ranging from 2,000 to 24,000 units/min with a reperfusion efficacy of 60—89% (108—112). In another urokinase trial, 2.0 million units were adrninistered intravenously, resulting in a thrombolytic efficacy of 60% (113). Effectiveness in terms of reduction in mortaUty rate has not been deterrnined because of the small number of patients studied. 

Tinidazole, a second-generation nitroimidazole with protozoal and anaerobic activity, has been available outside the United States for over 30 years.18 Recently, the Food and Drug Administration (FDA) approved it for use in the United States. As a single 2-g dose, tinidazole has an efficacy equivalent to a 2-g dose of metronidazole. Tindazole also has a longer half-life than metronidazole, 14 and 7 hours respectively, and penetrates into male reproductive tissue better than metronidazole. 

The main potential utility of the pure antiestrogens is in the treatment of breast cancer. Several studies on their effects on the breast demonstrate both the pure antiestrogenic action of the tested compounds and their beneficial effects on breast cancer treatment. In experiments conducted in nude mice xenotrans-planted with two different human estradiol-dependent breast tumors, a single injection of fulvestrant provided an antitumor efficacy equivalent to that of daily tamoxifen treatment for at least 4 weeks (Wakeling et al. 1991). Additionally, RU 58668 was able to induce up to 30% disappearance of MCF-7 breast... 

Artemisinins are also proving to have outstanding efficacy for the treatment of complicated falciparum malaria. Large randomized trials and meta-analyses have shown that intramuscular artemether has an efficacy equivalent to that of quinine and that intravenous artesunate is superior to intravenous quinine in terms of parasite clearance time and—most important—patient survival. Intravenous artesunate also has a superior side-effect profile compared with that of intravenous quinine or quinidine. Thus, intravenous artesunate will likely replace quinine as the standard of care for the treatment of severe falciparum malaria, although it is not yet widely available in most areas. Artesunate and artemether have also been effective in the treatment of severe malaria when administered rectally, offering a valuable treatment modality when parenteral therapy is not available. 

Valproic acid (valproate), discussed in detail elsewhere as an antiepileptic (see Chapter 24 Antiseizure Drugs), has been demonstrated to have antimanic effects and is now being widely used for this indication in the USA. Overall, it shows efficacy equivalent to that of lithium during the... 

Herrmann G, Steeger D, Klasser M, Wirbitzky J, Furst M, Venbrocks R, Rohde H, Jungmichel D, Hildebrandt HD, Pamham MJ, Gimbel W, Dirschedl H. Oxaceprol is a weU-tolerated therapy for osteoarthritis with efficacy equivalent to diclofenac. Clin Rheumatol 2000 19(2) 99-104. 

The signs and symptoms described are typical of withdrawal from physical dependency on an opioid that has efficacy equivalent to a full agonist—in this case, meperidine. Although anxiety, agitation, i... 

Several clinical studies have shown buspirone (14a) to have anxiolytic efficacy equivalent to that of DZ with significantly less sedation. ° Rats trained to discriminate oxazepam or pentobarbital from vehicle did not generalize to buspirone. At doses above those which are anxiolytically relevant in man, the drug caused a dose-related elevation of plasma prolactin in male subjects, and like the BZ s also increased growth hormone levels. Buspirone elicits a dose-dependent rise in rat striatal dopamine (DA) metabolite levels and may do so by selective antagonism of presynaptic DA autoreceptors with minimal postsynaptic effects. Its catalepsy-reversal effects may occur... 

DCC dichloroisocyanurate, which demonstrated efficacy equivalent to chlorine in testing. ... 

Antidepressive activity was noted for some tricyclic compounds having a six-membered central ring. A series of naphthyrldones, C-29 C-42 ( ). and C- 5 (7c). caused inlpramine—like activity in animals. The Influence of on central biogenic amine levels," as well as its absorption, distribution and excretion, was Investigated in mice and rats. Several phenothiazine derivatives had antidepressive activity. In extensive clinical trials fluoracizine (8a). a CPj analog of chloracizine, showed antidepressive efficacy equivalent to imipramine. 

Class III Premarket Approval. Similar to a new dmg approval, a premarket approval grants the appHcant a Hcense to market a specific weU-characterized device. These devices are subject to the requirements of Section 515 of the Eood, Dmg, and Cosmetic Act. A post-amendment device is a device put ia commercial distribution after May 28, 1976. If it is not substantially equivalent to a preamendment device it is automatically ia Class 111, and a premarket approval appHcation (PMA) is required. The appHcation must iaclude reports of preclinical and clinical studies done ia support of claims of safety and efficacy as well as any labeling claims made for the device. Once the PMA is submitted, the PDA determines whether the appHcation iacludes the required information. If the PMA is suitable for scientific review, the PDA has 180 days from the filing date to approve or deny the appHcation. Polybutester, polydioxanone, polyglyconate, and ePTPE sutures are all regulated as Class 111 devices. 

The most convenient method is the formation of two equivalents of (25) by retro-aldol cleavage from commercially available (26) by the combined action of FruA and triose phosphate isomerase (Figure 10.18 inset) [84]. This scheme has been extended into a highly integrated, artificial metabolism for the efficacious in situ preparation of (25) from inexpensive feedstock such as glucose and fructose (two equivalents of... 

Jacobson IM, Everson GT, Gordon SC, Kauffman R, McNair L, Muir A, McHutchison JG (2007) Interim analysis results from a phase 2 study of telaprevir with peginterferon alfa-2A and ribavirin in treatment-naive subjects with hepatitis C. AASLD 58th Annual Meet, Abstract 177 Johnson M (2006) Response to Atazanavir/ritonavir versus lopinavir/ritonavir equivalent or different efficacy profiles by HUl. AIDS 20 1987... 

Further SAR studies on the cyclopentane scaffold have included variation of the hydrophobic side-chain to incorporate a carboxamide substituent (Chand et al. 2004), equivalent to the C6-carboxamide derivatives of zanamivir, and extension of the length of the hydrophobic side-chains (Chand et al. 2005a). Analogues that incorporate a longer 4-heptyl side-chain showed comparable efficacy to 34 upon oral and intranasal administration in mice, and comparable or better efficacy than oseltamivir and zanamivir (Chand et al. 2005a). 

Lawrence et al. [66] in a split face study, compared the efficacy and safety of Jessner s solution and 35% TCA with 5% fluorouracil in the treatment of widespread facial actinic keratoses. Fifteen patients were treated. Both treatments reduced the number of visible actinic keratoses by 75%. Similarly, both caused equivalent reductions in keratinocyte atypia, hyperkeratosis, and parakeratosis. Compared to fluorouracil, only one application of the peel was necessary. 

The efficacy of DA agonists, even if not total, does show that striatal function can be reinstated to some extent by merely flooding it with the equivalent of DA and that this does not have to be released physiologically. 

A complete dose-response analysis was generated for PCP for doses from 0.625 to 20 mg/kg IP (data not shown). PCP exhibited dose-related anticonvulsant action when day one minus day three differ ence scores were compared for all doses tested. When retested with saline only on day five, no reduction in convulsant sever it or super-sensitive response was observed (day one minus day five), indicating no carryover drug effect 48 hours after dosing. At behavioral ly equivalent doses, all compounds assayed were clearly anticonvulsant (table 3). TCP was most potent at the doses tested. PCA was the most efficacious, and reduced convulsant severity by 2.58 points. As with PCP, none of the other phencycli-noids had any carryover effects 48 hours after dosing (day one minus day five). 

Conventional therapy prior to the advent of HP eradication therapy consisted of standard doses of sucralfate or an H2RA for 6 to 8 weeks. A PPI provides equivalent efficacy with a treatment duration of only 4 weeks. Long-term antiulcer therapy is ineffective for treating HP infections. 

Doses should be titrated at intervals no more frequent than every 2 to 3 days. Because spironolactone is used for its antialdosterone effects, much higher doses (up to 400 mg/day) are used than those used when treating hypertension. If intolerable side effects such as gynecomastia occur with spironolactone, other potassium-sparing diuretics may be used, but clinical trials have not shown equivalent efficacy.22... 

Recent studies show equal efficacy of equivalent doses of intravenous and oral dosage forms.30,31 Some clinicians are now using oral prednisone for patients experiencing relapses to avoid the discomfort, inconvenience, and expense of intravenous therapy. 

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