Monotherapy

In the treatment of hypertension, ACE inhibitors are as effective as diuretics, (3-adrenoceptor antagonists, or calcium channel blockers in lowering blood pressure. However, increased survival rates have only been demonstrated for diuretics and (3-adrenoceptor antagonists. ACE inhibitors are approved for monotherapy as well as for combinational regimes. ACE inhibitors are the dtugs of choice for the treatment of hypertension with renal diseases, particularly diabetic nephropathy, because they prevent the progression of renal failure and improve proteinuria more efficiently than the other diugs. 

Three fungal infections - Madura feet (mycetoma), chromomycosis and sporotrichosis - fall into the category of subcutaneous mycoses, their distribution is mainly in tropical and subtropical areas. The ideal treatment for madura feet caused by fungi is not yet established the azoles are of some benefit, however, neither the optimal drug, dose, nor the treatment schedules are known. Chromomycosis responds well to ITRA monotherapy or the combination of 5FC plus ITRA. ITRA has been set up as standard therapy for cutaneous and lymphatic sporotrichosis. 

Antiprotozoal Drugs. Figure 5 Artemisinin combination therapy (ACT) Adding a 3-days artesunate course to mefloquine cleats the parasitaemia much more rapidly (A — A). The remaining parasites are exposed to higher mefloquine levels in ACT (B) compared to mefloquine monotherapy (B (with permission White, 1997 Antimicrob Agents Chemother 41 1413-1422). 

The broadest spectrum of antiviral diugs is available against HIV. However, monotherapy with any of these diugs leads to rapid treatment failure due to selection and further evolution of resistant viruses. Since acquisition of resistance mutations requires vims replication,... 

Treatment for tumor patients with synthetic drags -chemotherapeutics - that may be of completely different chemical structure. The main goal of tumor chemotherapy is to achieve a selective toxicity for the tumor without causing damage to the host, for instance by combining several cytostatic drags at doses lower than required for monotherapy. 

Interferons. Table 1 Approved indications for interferon therapy either as adjuvant or for monotherapy... 

Similar to HBV, infections with hepatitis C virus (HCV) have a high rate of progression from an acute to a chronic state that frequently leads to cirrhosis or hepatocellular carcinoma [2]. Monotherapy for HCV infection with IFN-a or combined therapy with ribavirin and IFN-a is associated with initial rates of response as high as 40%. The rates of sustained responses are, however, lower and also depend on the viral genotype. In patients infected with HCV genotype 2 or 3, the response was maximal after 24 weeks of treatment, whereas patients infected with genotype 1 -the most frequent in the USA and Europe - required a minimum treatment course of 48 weeks for an optimal outcome. 

So far, five different protease inhibitors have been approved by the FDA for the treatment of HIV infection [3, 4]. Clinical trials in which protease inhibitors were evaluated in monotherapy demonstrated the potency of this class of inhibitors (decrease in HIV RNA levels, increase in CD4 cell counts). Treatment regimens were subsequently broadened to include reverse transcriptase inhibitors in combination with protease inhibitors. The result of these clinical trials has led to a list of guidelines with recommendations for the optimal treatment options. Prolonged control of the infection with combination therapy (highly active antiretroviral therapy, HAART ) could be shown. 

Nelfinavir is a nonpeptidic, rationally designed HIV protease inhibitor. Nelfinavir has demonstrated efficacy in both monotherapy and in combination with the reverse transcriptase inhibitors stavudine (d4T) or zivudine + 3TC. The major side effect is mild to moderate diarrhea. 

The topical corticosteroids are contraindicated in patients with known hypersensitivity to the drug or any component of the drug, as monotherapy for bacterial skin... 

Saquinavir. SQV was first shown in vitro to have potent HIV-1 inhibition in acutely infected cells with an IC50 in the subnanomolar range and to inhibit viral maturation in chronically infected cells at 10 nM (Craig et al. 1991). Subsequently, clinical trials with SQV monotherapy in HIV-1 infected men at concentrations up to 600 mg three times a day for 16 weeks resulted in a decrease in HIV-1 RNA of 80% (0.71ogio) (Kitchen et al. 1995). These and other data facilitated SQV in becoming the first FDA-approved PI in December 1995. In its original formulation. 

Gruzdev B, Rakhmanova A, Doubovskaya E, Yakovlev A, Peelers M, Rinehart A, de Dier K, Baede-van Dijk B, Parys W, van t Klooster G (2003) A randomized, double-bhnd, placebo-controlled trial of TMC125 as 7-day monotherapy in antiretroviral n Ve, HIV-1 infected subjects. AIDS 17 2487-2494... 

Herandez J, Amador L, Amantea M, Chao H, Hawley P, Paradise L (2000) Short-course monotherapy with AG1549, a novel non-nucleoside reverse transcriptase inhibitor (NNRTI), in antiretroviral naive patients. In 7th conference on retroviruses and opportunistic infections. San Francisco, CA, Abstract 669... 

Pharmacokinetic studies demonstrated good oral bioavailability of maraviroc and a terminal half-life of 16-23 h following multiple dosing (Abel et al. 2003 Walker et al. 2005). Single doses of up to 900 mg and multiple doses of up to 300 mg BID for 28 days were well tolerated (Abel et al. 2003 Russell et al. 2003 Walker et al. 2005). In Phase 2a studies, treatment-naive HIV-1 patients with R5 virus who received maraviroc monotherapy at doses ranging from 25 mg QD to 300 mg BID for 10 days experienced a median viral load reduction of 1.64 log jg copies/mL and... 

Two orally bioavailable compounds that target HIV-1 attachment have been described. BMS-806 and BMS-043 bind to gpl20 (reviewed by Kadow et al. 2006) and demonstrate variable activity when tested in vitro against panels of virus isolates (Lin et al. 2003). BMS-043 has shown efficacy in short-term monotherapy studies... 

Kitrinos K, Labranche C, Stanhope M, Madsen H, Demarest J (2005) Clonal analysis detects preexisting R5X4-tropic virus in patient demonstrating population-level tropism switch on 873140 monotherapy. Antivir Ther 10 S68... 

Lalezari J, Thompson M, Kumar P, PUiero P, Davey R, Patterson K, Shachoy-Clark A, Adkison K, Demarest J, Lou Y, Berrey M, Piscitelh S (2005a) Antiviral activity and safety of 873140, a novel CCR5 antagonist, during short-term monotherapy in HIV-infected adults. Aids 19 1443-1448... 

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