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1.
Antimicrob Agents Chemother ; 30(5): 729-32, 1986 Nov.
Article in English | MEDLINE | ID: mdl-3800349

ABSTRACT

The pharmacokinetics of intravenously administered flucloxacillin (2.0 g to five volunteers) are described. The passage of flucloxacillin to peripheral lymph and suction skin blisters was monitored. This drug was selected because the high serum protein binding of 96% offered a particularly good opportunity for the study of the impact on tissue penetration. Flucloxacillin was assayed by high-pressure liquid chromatography, and pharmacokinetics were assayed by computerized curve fitting to accepted models. Penetration of flucloxacillin to extravascular foci was rapid. After 30 min the drug concentrations were 0.5 +/- 0.3 microgram/ml in lymph and 0.9 +/- 0.7 microgram/ml in blister fluid. The peak concentration was 11.7 +/- 5.6 micrograms/ml in lymph and 4.6 +/- 1.4 micrograms/ml in blister fluid. Concentrations in urine were above 111 +/- 50 micrograms/ml throughout the 8-h monitoring period, and urinary recovery was 60.4%. The half-life was 2.1 +/- 0.9 h in serum, 1.4 +/- 0.6 h in lymph, and 11.0 +/- 4.1 h in blister fluid. The differences in half-life were significant (P less than 0.05) between serum and blister fluid but not between lymph and serum. Penetration, as represented by the mean ratios of areas under the curve, was 19.7 +/- 8.1% to lymph and 38.2 +/- 11.7% to blister fluid. The flucloxacillin distribution volume during the phase of elimination was 36.4 +/- 16.0 liters and the total body clearance was 12.9 +/- 5.5 liters. Flucloxacillin showed good tissue penetration, considering its very high serum protein binding. High flucloxacillin levels in lymph and blister fluid were explained in part by drug affinity to extravascular albumin. The major impacts of high protein binding are (i) slightly slower passage into extravascular sites, (ii) slightly later peak concentration, and (iii) levels in extravascular fluid that are persistently below those in serum.


Subject(s)
Blood Proteins/metabolism , Capillary Permeability , Cloxacillin/analogs & derivatives , Floxacillin/metabolism , Adult , Female , Humans , Kinetics , Lymph/metabolism , Male , Protein Binding
3.
Chemotherapy ; 32(4): 319-28, 1986.
Article in English | MEDLINE | ID: mdl-3731918

ABSTRACT

The penetration into suction skin blisters and pharmacokinetics of 4 sulfonamides (sulfacarbamide, sulfadimidine, sulfadiazine, sulfamethoxazole) and two dihydrofolate reductase inhibitors (methioprim, trimethoprim) have been compared in healthy volunteers. The concentrations were monitored after the first dose and for the subsequent 4 days when approximate steady state conditions could be assumed to have been established. The serum or plasma half-life of the agents in the above order was 3.1, 6.3, 13.9, 12.1, 9.3, and 12.0 h. The respective areas under the serum curves were 97.1, 607.8, 942.6, 1423.1, 128.1 and 175.4 mg/l per dose of 1.0 g. With the sulfonamides, there was a distinct correlation between serum protein binding and pKa and the ability of the compounds to penetrate into blister fluid as shown by the 12-hour ratios between areas under the concentration curves in blister fluid relative to serum.


Subject(s)
Blister/metabolism , Folic Acid Antagonists , Sulfonamides/metabolism , Adult , Body Fluids/metabolism , Female , Half-Life , Humans , Kinetics , Male
4.
Scand J Dent Res ; 92(4): 344-51, 1984 Aug.
Article in English | MEDLINE | ID: mdl-6591370

ABSTRACT

Twenty-four adults participated in an intraindividual crossover experimental study to compare the plaque removing ability of straight multitufted and V-shaped brushes. Twelve of the participants had loss of periodontal tissue resulting in open but healthy interdental areas while the other 12 displayed no periodontal breakdown. In part 1 the participants were asked to brush their teeth using their own brushing technique and length over two 12-day periods during which time they, at random, used one brush for the first and the other brush for the second period. In part 2 the participants were professionally brushed by two dental assistants using four brushing techniques (The Bass, The Roll, The Circular Scrub and The Horizontal Scrub) randomly assigned to the four quadrants of the mouth. Cleaning was performed once a day for two 5-day periods, during which time the participants refrained from brushing and interdental cleaning. Initial toothbrush assignment was randomized. At the beginning of the study and each test period no plaque or gingival inflammation was visible. At the end of each period the accumulated plaque was registered. The results showed that there was no difference between the two brushes tested in the unsupervised part. The plaque removing ability when using either of the brushes varied between participants. When professionally used the straight multitufted and V-shaped toothbrushes did not show any difference in plaque removal on buccal and lingual surfaces. Interproximally the V-shaped toothbrush was better at plaque removal than the straight one.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Dental Plaque/prevention & control , Toothbrushing/methods , Adult , Dental Plaque Index , Dental Prophylaxis , Equipment Design , Humans , Middle Aged , Oral Hygiene , Toothbrushing/instrumentation
6.
Acta Med Scand ; 212(1-2): 11-5, 1982.
Article in English | MEDLINE | ID: mdl-7124456

ABSTRACT

Toxicokinetic studies during hemodialysis are presented in two patients with blood ethylene glycol concentrations of 40 and 41 mmol/l, respectively. Treatment involved bicarbonate, ethanol and hemodialysis with a 1.6 m2 dialysator. Both patients developed acute renal failure and one was discharged with permanent cerebral impairment. The other made an uneventful recovery. The average dialysator clearance of ethylene glycol at a blood flow of 200 ml/min was 145 and 148 ml/min, respectively. Assuming a volume of distribution of ethylene glycol of 0.7 l/kg, the dialysator represented about 92 and 95%, respectively, of the total body clearance of ethylene glycol during ethanol treatment. During hemodialysis a blood ethanol concentration of about 15 mmol/l (0.7 g/l) caused a near complete inhibition of ethylene glycol metabolism at ethylene glycol concentrations up to about 25 mmol/l (1.6 g/l). We recommend prompt hemodialysis in ethylene glycol poisoning to supplement alkali and ethanol treatment.


Subject(s)
Ethylene Glycols/poisoning , Acute Kidney Injury/chemically induced , Adult , Bicarbonates/therapeutic use , Brain Damage, Chronic/chemically induced , Ethanol/therapeutic use , Ethylene Glycols/blood , Humans , Inactivation, Metabolic , Male , Metabolic Clearance Rate , Middle Aged , Renal Dialysis
9.
Antimicrob Agents Chemother ; 19(1): 82-5, 1981 Jan.
Article in English | MEDLINE | ID: mdl-7247364

ABSTRACT

Various sulfonamides and trimethoprim were given orally twice a day to healthy volunteers. The drug concentrations in serum and tissue fluid from skin blisters were determined concomitantly. Maximal serum concentrations were obtained after 1 to 3 h. Absorption of sulfacarbamide and sulfadimidine was more rapid than for sulfadiazine, sulfamethoxazole, and trimethoprim. The penetration to blister fluid was delayed and maximal concentrations were usually reached after 4 to 8 h. The highest penetration to blister fluid was found for sulfacarbamide, sulfadiazine, and trimethoprim. During maintenance therapy sulfadiazine and trimethoprim gave blister fluid concentrations usually above 50% of the serum level. However, on the basis of dosage the highest sulfonamide concentration both in serum and blister fluid was obtained with sulfamethoxazole.


Subject(s)
Blister/metabolism , Exudates and Transudates/metabolism , Sulfonamides/metabolism , Trimethoprim/metabolism , Adult , Female , Humans , Kinetics , Male , Skin/metabolism , Sulfonamides/blood , Time Factors , Trimethoprim/blood
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