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RESULTS Staphylococcal mouse wound infections. i ; Comparison of mupirocin cream with mupirocin ointment and their respective vehicle placebos. At day 5, the mean bacterial counts for wounds treated with mupirocin formulations were significantly lower than those for their respective vehicle placebos P 0.001 ; , and there were no significant differences between placebos and untreated controls Table 3 ; . Mupirocin cream had eradicated S. aureus Sweeting from 4 of the 10 treated wounds 10 CFU ; and reduced the mean count to 2.51 1.69 log10 CFU wound. Therapy with mupirocin ointment reduced the mean count to 4.62 2.15 log10 wound; of the eight evaluable wounds, three 38% ; had bacterial counts of 2.50 log10 CFU wound or less, while the five remaining wounds contained 5 to 6 log10 CFU wound and levofloxacin.

Nine clearance r2 0.86, t 9.281, P 0.001; see Fig. 3 ; The creatinine clearance reported was obtained within 1 day \ \ of study period. The time varied for each subject, but X: z 1.4' .z o , - usually corresponded to study day 4. In two subjects, . * - . * C-, LLX creatinine r ; * \, v of the clearance was determined in conjunction with two z 0 * study periods; both are reported. L' 1.2 J The unbound fraction of sulfisoxazole was higher in the renal transplant patients than in the control subjects, both on day 1 and on the last study day t 2.489, P 0.05, and t 4.215, P 0.001, respectively ; . The difference on day 1 1.0 | * U * .-mNu wf \ appears to correspond to the difference in albumin concentration between these groups 3.8 versus 4.4 g dl; t 3.370, n 0.s * P 0.01 ; . Calculating nK from the relationship: f, 1 + nK. Pt ; , wheref, is the unbound fraction, n is the number of CZ ; A binding sites, K is the association constant for albumin , 0.66 A * * sulfisoxazole, and P, is the albumin concentration, and z. * comparing the obtained values for nK between the groups, F 0.4 l . * - * -- * no differences could be found t 0.918, P 0.30 ; . This , - relationship is based on the assumption that only a small UA * fraction of the albumin sites are occupied. The higher 0.2, 0 unbound fraction on the last study day, on the other hand, cannot be explained by the albumin concentration difference l I I alone, as a significant difference in nK values between the 2 4 6 groups was found t 3.362, P 0.01 ; . The excretion of sulfisoxazole from urine, on average, TIME, DAYS appeared to increase with time. The increase seemed to FIG. 2 Average recovery from urine with time of sulfisoxazole correspond to an improvement in the renal function, as 0 ; , connbined sulfisoxazole and N4-acetyl sulfisoxazole A ; , evidenced by the decreasing creatinine concentration in and total sulfisoxazole determined by the Bratton-Marshall 5 ; serum with time. An exception appeared to occur between method i ; . Average creatinine values in serum, calculated as days 6 and 10, when patient no. 6 experienced a rejection n nl , 1 'CR, ; , are plotted for comparison - ; . period, resulting in a significantly increased creatinine level i 1 in serum. The excretion of sulfisoxazole from urine correlated with 0.04 101 ; . With the assumption that the bioavailability is the creatinine concentration in serum in only two of the similar lIn renal transplant patients, the values in Table 3 transplant patients no. 2 and 6; P 0.025 by the Student t were tre, ated as the clearance values. test ; . The total unbound clearance CLu ; , as well as the unbound renal clearance CLuR ; , were statistically significantly DISCUSSION lower in the transplant patients than in the control subjects t 2.286, P 0.05, and t 3.199, P 0.01, respectively ; . The elimination of sulfisoxazole CLu ; in renal transplant The unbound extrarenal clearance CLuxR ; and the unbound patients is similar to that found in normal subjects when formation clearance of N4-acetyl sulfisoxazole in the transdifferences in renal function are taken into consideration. plant patients were, on the other hand, not statistically There is no evidence of reduced metabolic elimination significantly different from the control values t 0.265, P similar to that suggested by Reidenberg et al. 11 ; in renal 0.70, and t 1.324, P 0.20, respectively ; . The lower CLu failure subjects or to what was found in renal failure animals therefore seems to be a result of the decreased renal elimi 9a ; . This is probably a consequence of only a moderately nation of sulfisoxazole. The CLUR of sulfisoxazole in the reduced renal function in our patients compared with those study subjects correlated highly with the measured creatiin the other studies. Prescribing, from page 1 be considered. If a patient misses a once-daily dose, they miss an entire day of therapy. If only one dose of a twice-daily dose is missed, they are "partially" treated for that day. One study showed that days without dosing were observed twice as frequently with the once-daily dosing compared with a twice-daily regimen. There is also the issue of medication "forgiveness" for noncompliance. The forgiveness period is the time that a medication's effect persists after a dose is missed. If a medication's duration of effect is more than 12 hours but less than 24 hours, it needs to be given twice a day. The patient will receive a therapeutic effect for more that the 12 hour dosing interval. The forgiveness period equally applies to both oncedaily and twice-daily medications. Patients use cues to remind them when to take their medications eg, breakfast, dinner, bedtime ; . When the cues are changed or interrupted and lexapro.

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