Penetration of Trimethoprim and Sulfadiazine into Sinus Secretion in Acute Maxillary Sinusitis

Mattila, J.; Männistö, Pekka T.; Luodeslampi, M

doi:10.1159/000238193

Cited by 3 publications

(3 citation statements)

References 15 publications

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“…The distribution in nasal secretions was studied by Ullmann et al (1983) who gave 1.0g co-trimazine to 20 healthy volunteers for 4 days. The AUC in nasal fluid was 140% of that in the serum in the case of sulphadiazine and 300% for trimethoprim, these values being similar to those reported by Mattila et al (1983). The concentrations present in nasal fluid exceeded the minimum inhibitory concentrations of the more commonly isolated respiratory tract pathogens throughout the dosage intervals.…”

Section: Distributionsupporting

confidence: 85%

Clinical Pharmacokinetics of Co-Trimazine

Bergan¹,

Örtengren²,

Westerlund³

1986

Clinical Pharmacokinetics

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The clinical pharmacokinetics of co-trimazine (trimethoprim plus sulphadiazine) are reviewed and compared with those of co-trimoxazole (trimethoprim plus sulphamethoxazole). Both combination drugs have similar serum half-life values in persons with normal renal function (half-life of 8 to 12 hours), but the sulphamethoxazole metabolites are retained more than trimethoprim in reduced renal function. Sulphadiazine is less metabolised and the total sulphonamide load of therapeutic doses of co-trimazine is therefore less than for co-trimoxazole. Both co-trimazine and co-trimoxazole have high bioavailability. A suspension of co-trimazine gives serum concentrations comparable with those of tablets. The extravascular penetration of the co-trimazine components is reflected by the total area under the lymph concentration curve in comparison with serum. This measure shows a penetration into peripheral human lymph of 68% for sulphadiazine and 59% for trimethoprim. The proportions eliminated in urine are about 55% for sulphadiazine, 30% for its acetylated metabolite and 75% for trimethoprim. In comparison, for co-trimoxazole, the proportion of sulphamethoxazole eliminated in urine is 15%, that of the acetylated derivative 47%, and that of trimethoprim is also 75%. Urine concentrations of both combinations have similar bioactivity against urinary pathogens after 500 mg of co-trimazine and 960 mg of co-trimoxazole.

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Section: Distributionsupporting

confidence: 85%

Clinical Pharmacokinetics of Co-Trimazine

Bergan¹,

Örtengren²,

Westerlund³

1986

Clinical Pharmacokinetics

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“…Like several previous studies with other tissues, our findings confirmed that extravascular TMP concentration exceeds that simultaneously present in serum [7][8][9][10]. TMP levels now measured in bile were, however, considerably higher than those reported earlier [2], Although an avid lipid solubility of TMP is the basis for good tis sue penetrance, this does not entirely ac count for its accumulation in bile and gall bladder.…”

Section: Discussionsupporting

confidence: 89%

Trimethoprim and Sulfadiazine Penetration into Bile and Gallbladder in Acute Cholecystitis

et al. 1987

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The concentrations of trimethoprim (TMP) and sulfadiazine (SDZ) in serum, bile and gallbladder wall of 9 patients with acute cholecystitis were measured after b.i.d. treatment with 160 mg of TMP + 500 mg of SDZ. The samples were collected 2–4 h after the last dose. Mean TMP concentrations were 1.71 ± (SE) 0.51 μg/ml, 4.53 ± 5.26 μg/ml and 2.31 ± μg/g in serum, bile and gallbladder, respectively. Mean SDZ concentrations were 22.2 ± 14.9 μg/ml in serum, 9.37 ± 8.99 μg/ml in bile and 16.1. ± 10.1 μg/g in gallbladder. The average ratios of bile-serum and gallbladder-serum concentrations were 2.64 and 1.35 for TMP and 0.42 and 0.73 for SDZ. There was a significant correlation between serum and gallbladder concentrations of both TMP and SDZ. No correlation existed between serum and bile levels.

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“…Salivary: serum trimethoprim ratios are 0.87 ± 0.2 (Watson & Stewart 1986); the sinus secretion: serum ratio is 1.33 for trimethoprim and 0.2 for sulphadiazine (Mattila et al 1983). Penetration of co-trimoxazole into breast milk is similar to that into saliva (Arnauld et al 1972), and into aqueous humour is 20% and 30%, respectively, of serum concentrations of trimethoprim and sulphamethoxazole (Salmon et al 1975).…”

Section: Distributionmentioning

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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Penetration of Trimethoprim and Sulfadiazine into Sinus Secretion in Acute Maxillary Sinusitis

Cited by 3 publications

References 15 publications

Clinical Pharmacokinetics of Co-Trimazine

Clinical Pharmacokinetics of Co-Trimazine

Trimethoprim and Sulfadiazine Penetration into Bile and Gallbladder in Acute Cholecystitis

Clinical Pharmacokinetics of Enzyme Inhibitors in Antimicrobial Chemotherapy

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