Trimethoprim with sulphamethoxazole

The concept of clinical synergism, which m be extremely difficult to demonstrate convincingly. Even with trimethoprim plus sulphamethoxazole, where tme synergism occurs in vitro, the optimum ratio of the two components may not always be present in vivo, i.e. at the site of infection in a particular tissue. 

Oiatton JY, Munafo Chave JP, Steinhauslin F, Roch-Ramel F, Glauser MP, Biollaz J. Trimethoprim, alone of in combination with sulphamethoxazole, decreases the renal excretion of zidovudine and its ghicuronide. BrJ Clin Pharmacol (1992) 34,551—4. 

Oral dosing of 5 subjects with 800 mg of sulphamethoxazole and 160 mg of trimethoprim twice daily, produced minimum steady-state plasma concentrations of about 55 pg/ml of sulphamethoxazole and 1.7 pg/ml of trimethoprim, on the ninth day (P. Kremers et al., J. clin. Pharmac., 1974, /4,112-117). 

For further references to trimethoprim when administered with sulpha-methoxazole, see under Sulphamethoxazole. 

BerganT, Brodwall EK,Vik-Mo H, Anstad U. Pharmacokineticsof sulphadiazine, sulphamethoxazole and trimethoprim in patients with varying renal function. Infection. 1979 7 SuppI 4 S382-7. 

Prophylaxis against Pneumocystis carinii, classified as a fungus although in many ways it behaves more as a protozoal infection, should be with trimethoprim-sulphamethoxazole. However, it should be borne in mind that this can cause bone marrow suppression in its own right. 

SrinivasNR,Kni5)pCA,BatteigerB, Smith R BarbhaiyaRH. A pharmacokinetic interaction study of didanosine coadministered with trimethoprim and/o sulphamethoxazole in HIV seropositive asymptomatic male patients. BrJ CUn Pharmacol (199 41,207-15. 

The simultaneous dissolution profile of two compounds with overlapped spectra has been solved using different mathematical approaches. Derivative spectrophotometry is a solution used for the couples sulfadiazine-trimethoprim, amitriptyline-perphenazine, sulphamethoxazole-trimethoprim, amoxicilline-bromhexine, and amoxicillin-clavulanic acid. This strategy has been used to obtain three dissolution profiles, namely, the standard (global) profile and two individual profiles such as sulphamethoxazole-trimethoprim or hydrochlorothiazide-captopril. 

The combination of a sulphonamide with trimethoprim (Wellcome and Roche, 1968), an inhibitor of microbial dihydrofolate reductase, blocks two steps in the synthesis of tetrahydrofolate and leads to a synergistic antibacterial effect. Trimethoprim sulphamethoxazole combinations (Figure 4.22) continue to play an important role in antibacterial therapy (Table 4.4) but as a... 

A 41-year-old woman with systemic lupus erythematosis developed methemoglobinemia 2 days following administration of trimethoprim-sulphamethoxazole (40/400mg) for prophylaxis of pneumocystis pneumonia [139 ]. 

Sulphamethoxazole ( Gantanol 3-p-aminobenzenesulphonamido-5-me-thylisoxazole) has been selected for use with trimethoprim for sequential blocking (Section 9.5), because both drugs have similar distribution and duration. 

---