Combined therapies case studies

In another study of 19 patients with complete or near-complete (TIMI grade 0 or 1) middle cerebral artery (MCA) occlusion, combination therapy with reduced-dose rt-PA and tirofiban infusion was associated with recanalization in 68% of patients, significant reductions of MRI ischemic lesion volumes, and substantial clinical improvement (median NIHSS change from 17 at baseline to 2 after treatment, p = 0.002). No cases of sICH occurred. 

Preclinical studies suggest mold-active azoles plus echinocandins have enhanced activity against Aspergillus A. terreus should be considered resistant to amphotericin B Activity of amphotericin B and voriconazole is decreased versus Aspergillus species higher doses or combination therapy may be indicated in more refractory cases... 

In a classic case of serendipity, cisplatin (PLATINOL ), a key component of the combination therapy which revolutionised treatment of testicular cancer [ 1 ], was uncovered fortuitously in the 1960s during studies on the effect of an electric current on the growth of E. coli [ 17,18]. Cell division was inhibited not by the electric current but by production of a platinum complex from the... 

This subject has been reviewed in relation to combined oral therapy. In a systematic review of 63 studies with a duration of at least 3 months and involving at least 10 patients at the end of the study, and in which HbAlc was reported, five different classes of oral drugs were almost equally effective in lowering blood glucose concentrations (13). HbAic was reduced by about 1-2% in all cases. Combination therapy gave additive effects. However, long-term vascular risk reduction was demonstrated only with sulfonylureas and metformin. 

Combination therapy The combination of IFNa + lamivudine is superior to the corresponding monotherapy and it yielded considerably better results in patients who were resistent to IFN. (164, 166, 186, 195, 196) Likewise Peg-IFNa + lamivudine were applied with success. (182) A combination of lamivudine + ADV led to a virological and biochemical improvement during treatment up to 52 weeks (191, 192). In another study, however, therapy with IFNa + lobucavir (2 x 200 mg/day) had only little success. A combination of lamivudine + famciclovir sometimes produced a certain positive effect. (198) In the same way, IFNa + famciclovir improved initial values in some cases. (183) A combination of famciclovir + thymosin activates T-cell response in the immunotolerance phase. (174) The possibility that IFNa + acyclovir are synergistic in HBV infection has been suggested (S.w. ScHALM et al., 1985) acyclovir as monotherapy (45 mg/kg BW/day, i.v. infusion for 28 days) showed no benefit in chronic HBV carriers with stable disease. (152)... 

Changes in pharmacokinetics were studied in male Wistar rats when intravenous vancomycin 100 mg/kg and levofloxacin 20 mg/kg were administered together (124). There was an increase in the AUC and half-hfe of vancomycin. There was also an increase in the AUC and a delay in the t ax of levofloxacin, but no effect on Cmaxi these data suggested delayed absorption of levofloxacin. Concomitant administration had no effect on the correlation between serum and hepatic tissue concentrations of levofloxacin, but it markedly reduced the correlation between the serum and renal tissue concentrations of vancomycin. Vancomycin increased serum creatinine concentrations 8 hours after administration. However, there was no difference in animals who received monotherapy compared with animals who received combined therapy. The authors suggested the cautious use of a combination of levofloxacin and vancomycin and advised monitoring blood concentrations of vancomycin in such cases. 

In this case, the rmax, Cmax, AUC and the half time of elimination for parent drug and principal metabolites become the end-points of the study. For combination therapies, these endpoints have to be measured and fulfilled for all active components, and the therapies should not be administered separately. 

The most commonly encountered adverse and serious symptoms are hyperpyrexia, respiratory failure, and impaired consciousness (including coma and death). Even so, there are many published cases and studies that have not revealed any interaction between MAOis and meperidine. All in all, combined therapy is relatively contraindicated. The mechanism of the potentially fatal reactions is unknown. 

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