Pharmacokinetics of co-trimoxazole and co-tetroxazine in geriatric patients

Naber, K.; H, Vergin; Weigand, William A.

doi:10.1007/bf01640724

Cited by 9 publications

(3 citation statements)

References 12 publications

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“…The serum half‐life and drug excretion pattern paralleled the level of renal function. Naber et al showed similar findings in an earlier study of elderly patients 234 …”

Section: Pharmacology and Pharmacokinetics Of Antibioticssupporting

confidence: 75%

Antimicrobial Therapy for the Elderly Patient

Yoshikawa¹

1990

J American Geriatrics Society

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“…The serum half‐life and drug excretion pattern paralleled the level of renal function. Naber et al showed similar findings in an earlier study of elderly patients 234 …”

Section: Pharmacology and Pharmacokinetics Of Antibioticssupporting

confidence: 75%

Antimicrobial Therapy for the Elderly Patient

Yoshikawa¹

1990

J American Geriatrics Society

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“…The tvi of SDZ and TMP were longer in this study than in a previous one dealing with elderly [11]. There the mean lVl after the first dose of SDZ was 10.5 ± 1.2 h and of TMP 10.3+ 1.8 h, but with a mean age of 73.1 ± 2.9 years in that study [11] those subjects were on the average nearly a de cade younger than our group.…”

Section: Discussioncontrasting

confidence: 52%

Pharmacokinetics of Co-Trimazine (Sulphadiazine plus Trimethoprim) in Geriatric Patients

Bergan

Allgulander²,

Fellner

1986

Chemotherapy

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The study was aimed at analyzing the pharmacokinetics of sulphadiazine (SDZ) and trimethoprim (TMP) in geriatric patients and was carried out in two stages. The first stage compared 11 geriatric patients (68–89 years old) and 9 healthy volunteers (21–34 years old). Serum concentration and urine elimination were determined on day 4 after 12-hourly administration of 1 tablet of co-trimazine containing 410 mg sulphadiazine (SDZ) plus 90 mg trimethoprim (TMP). The mean serum concentrations of SDZ were significantly higher in the older subjects than in the volunteers after 1, 8 and 12 h (p < 0.05, 0.01, 0.01), but were not differentiable after 2 or 4 h. For TMP, the serum levels were higher (p < 0.05) in the patients only after 8 h. The amounts collected in urine were higher in the normal volunteers for SDZ during the intervals 0–2 h (p < 0.05), 2–4 h (p < 0.01), and 4–8 h (p < 0.01), but not for 8–12 h. The 12-hour recovery was 69% SDZ + acetyl-SDZ recovered in the patients compared to 66.0% in the volunteers. Indistinguishable amounts of TMP were recovered during each interval in the two groups of subjects, 59.2% in the patients compared to 70.0% in the volunteers. The second stage of the study comprised 9 geriatric patients of mean age 83.6 years and creatinine clearance 59.2 ml/min who were followed for 11 days. A steady increase in serum levels was observed. The mean peak serum concentration for SDZ was 16.7 ± 4.2 mg/l after the first dose and 44.7 ± 11.3 mg/l on day 10. For acetyl-SDZ, the respective concentrations were 2.1 ± 0.9 and 7.1 ± 3.1 mg/l. TMP rose from 0.79 ± 0.19 mg/l on the first day to 2.8 ± 1.3 mg/l on day 10. Parallel increases in urine elimination of SDZ, acetyl-SDZ and TMP were observed over the 11 days. After the first dose, the 12-hour urine elimination of SDZ corresponded to 16.2% of the dose, that of acetyl-SDZ to 7.5% and of TMP 21.5%. After the final dose, the respective 48-hour values were 103.2, 51.2 and 115%. The t_½ was 16.2 ± 5.6 h for SDZ, 25.5 ± 12.3 h for acetyl-SDZ, and 14.0 ± 6.0 h for TMP.

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“…Trimethoprim and tetroxoprim kinetics are unaltered in the elderly, but renal clearance of sulphamethoxazole and sulphadiazine is slightly decreased (Naber et al 1981). In contrast, renal clearance of sulphamethoxazole has been found to be comparable between elderly and young patients, whereas that of trimethoprim was significantly lower in the elderly (Varoquaux et al 1985), although total clearance was unaffected.…”

Section: Effects Of Agementioning

confidence: 93%

Clinical Pharmacokinetics of Enzyme Inhibitors in Antimicrobial Chemotherapy

Watson

Stewart

Platt

1988

Clinical Pharmacokinetics

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The effectiveness of some antimicrobial agents can be enhanced by using them in combination; such combinations are termed synergistic. Where one compound potentiates the effect of a second drug they may be coformulated. Inhibition of the bacterial degradation of an active antimicrobial is the basis of clavulanate and sulbactam-potentiated penicillin combinations, and inhibition of degradative pathways in the host is the rationale behind imipenem/cilastatin therapy. Trimethoprim/sulphonamide combinations depend on the maintenance of an effective ratio for synergistic action. In order to achieve potentiation the coformulated drugs should have similar pharmacokinetics. Trimethoprim was originally matched with sulphamethoxazole, since these two drugs have similar elimination half-lives, but the significantly poorer penetration of sulphonamides, their greater non-renal clearance, the emergence of resistance, and the adverse reactions attributable to them argue against the rationale that underlies their coformulation. Time-dependent inhibition of bacterial beta-lactamases by clavulanic acid and sulbactam has extended the use of penicillins which are highly susceptible to beta-lactamase inactivation. The beta-lactamase inhibitors must penetrate to the same extent as the penicillin used with them, and be present long enough to effect inhibition; thus, rapid penetration, similar or slower elimination and equivalent volume of distribution are necessary. These requirements are met for amoxycillin/clavulanic acid, ticarcillin/clavulanic acid and ampicillin/sulbactam combinations. Clavulanic acid is absorbed orally and is given with amoxycillin. However, since sulbactam is labile by this route, the combination of sulbactam with ampicillin to form the prodrug sultamicillin has been necessary to enable an oral form to be developed. Imipenem is metabolised by renal brush-border dehydropeptidases, and may cause proximal tubular necrosis. Cilastatin was designed to inhibit this metabolism, which it effectively does, thereby both potentiating the effect of imipenem and avoiding toxicity. Appropriate matching of the kinetics of coformulated drugs is intended to maximise potentiation and minimise the risk of emergent resistance. The kinetics of the above combinations are discussed in the light of these requirements and the effects of age and disease.

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Pharmacokinetics of co-trimoxazole and co-tetroxazine in geriatric patients

Cited by 9 publications

References 12 publications

Antimicrobial Therapy for the Elderly Patient

Antimicrobial Therapy for the Elderly Patient

Pharmacokinetics of Co-Trimazine (Sulphadiazine plus Trimethoprim) in Geriatric Patients

Clinical Pharmacokinetics of Enzyme Inhibitors in Antimicrobial Chemotherapy

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