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Ofloxacin: serum and skin blister fluid pharmacokinetics in the fasting and non-fasting state.

Using an agar well diffusion assay, the concentrations of ofloxacin were measured in serum and skin blister fluid after an oral dose of 300 mg given with or without a standardized meal. The apparent lag time was longer when the drug was taken with food than in the fasting state and the serum peak concentrations occurred later; the rates of absorption being 1.72 +/- 1.12/h (S.D.) and 3.40 +/- 1.56/h respectively. The mean peak concentrations of each individual in serum and blister fluid were 3.8 +/- 1.6 mg/l and 1.7 +/- 0.5 mg/l, respectively, when the drug was taken with food, compared with 4.2 +/- 1.9 mg/l and 2.1 +/- 0.7 mg/l in the fasting state. The rate of penetration into blister fluid was not influenced by the intake of food. The elimination half-life was 9.0 +/- 6.2 h in serum and 13.5 +/- 7.8 h in blister fluid when the volunteers were fasting. The corresponding values in the non-fasting state were 6.3 +/- 5.5 h and 10.6 +/- 4.6 h. The ratio of the area under the concentration versus time curve (AUC0-infinity) for blister fluid and serum was 1.20 +/- 0.70 when ofloxacin was given without food and 1.03 +/- 0.34 when given with the meal.

Adult↗

Pharmacokinetics of meropenem in serum and suction blister fluid during continuous and intermittent infusion.

The pharmacokinetics and penetration into suction blister fluid of meropenem was investigated after intermittent (10 mg/kg/6 h) and during continuous infusion (10 mg/kg/6 h) in eight healthy male volunteers in a crossover fashion. Concentrations in serum, urine and blister fluid were determined by a HPLC method. The pharmacokinetic parameters in serum (+/- S.D.) T1/2 beta, AUC and clearance after the third dose of intermittent infusion were 62.7 (11.4) min, 43.5 (7.1) mg.h/L and 292.1 (36.8) mL/min respectively. The penetration in blister fluid was rapid and good, with a AUC ratio blister fluid/serum of 84.7 (11.4)%. During continuous infusion, from 12 to 18 h after the start of the infusion, the mean concentration in serum was 6.3 (0.7, S.D.) mg/L and in blister fluid 5.4 (0.7, S.D.) mg/L. The clearance was 338.3 (45.6) mL/min for serum. Urinary recovery was 61.6 (8.7)% after intermittent and 61.9 (6.9)% after continuous infusion.

Adult↗

Biologic effect of blister fluid from thermal injuries on peripheral neutrophil chemotaxis.

Patients who become immunologically incompetent after major thermal injury often show in vitro defects in neutrophil function, including abnormalities of neutrophil chemotaxis. Although there is evidence suggesting that this acquired chemotactic defect is related to circulating suppressor substance(s) in the serum of these individuals, neither the etiology of this chemotactic defect nor the origin of these putative suppressors have been clarified. We report studies directed toward determining the biologic effect of blister fluid from thermally injured patients on peripheral neutrophil chemotaxis. Fifteen blister fluid samples from 12 patients were tested in attraction and inhibition assays of neutrophil chemotaxis. Chemotaxins were observed in all specimens. The biologic activity of blister fluid was similar to that produced by complement in serum and presumably was due to complement activity in the blister fluid. No inhibitors of chemotaxis were found in the blister fluid samples, although it seemed logical to expect to find suppressors in this fluid if they were generated locally by the thermal injury. Since suppressors were not found locally, other explanations must be sought to explain the etiology of the acquired defect in neutrophil chemotaxis that occurs after thermal trauma.

Blister↗

The effect of blister fluid from thermally injured patients on normal lymphocyte transformation.

Patients, after major thermal injury, often develop multiple in vitro immunologic abnormalities. The etiology of these immune defects is unknown, although there is evidence suggesting that these defects may be the results of circulating suppressor substance(s). To evaluate the role of the local injury in the development of immune incompetence the biologic effect of blister fluid from control lymphocyte mitogenic response to PHA was studied. Blister fluid from 35 patients, mean burn size 29% (range, 1-85% TBSA) was added to a standard lymphocyte blastogenic assay, using various concentrations of PHA (from 0.5 micrograms to 40 micrograms per well). Eight of these 35 patients (23%) had blister fluid which suppressed the control lymphocyte blastogenic response greater than 50%. Two patients with suppressive blister fluids also had suppressive serum. In contrast, only two of the nine patients whose blister fluid was not suppressive had suppressive serum. This suppressive activity was not related to bacterial contamination nor to the presence of detectable levels of endotoxin.

Adolescent↗

Blisters, cooling, antithromboxanes, and healing in experimental zone-of-stasis burns.

To appraise the ability of each to improve wound healing in zone-of-stasis burns (i.e., burns becoming progressively more ischemic early postburn), 1) an antithromboxane (dipyridamol PO immediately postburn), 2) burn-wound cooling, 3) their combination, or 4) no treatment was administered to burned guinea pigs half of which had burn blisters removed immediately postburn (PB). In all groups with blisters removed whole-thickness or very deep partial-thickness skin loss occurred. In all groups with blisters intact complete reversal of ischemia occurred without necrosis and, while dipyridamol and cooling each diminished stasis early PB, only cooled wounds showed any improved retention of hair follicles at 3 weeks PB. In this model, therefore: 1) blister removal eliminated any therapeutic effect of cooling or dipyridamol; 2) in burns with blisters intact, absorbed heat appeared at least as detrimental to healing as stasis, and 3) some of the beneficial effects of cooling appeared unrelated to prevention of stasis.

Animals↗

Management of blisters in the partial-thickness burn: an integrative research review.

Conflicting recommendations and clinical applications have been given concerning best practices for the management of burn blisters associated with partial-thickness burns. Arguments for the preservation of intact blisters center on the idea of naturally occurring biologic protection whereas the débridment of blisters has been advocated because of the perceived decreases in wound infection and complications. Recurring themes in burn wound management that are considered in this debate include infection, healing, functional and aesthetic outcome, patient comfort, ease of dressing care, and cost efficiency. The management of burn blisters should be supported by evidence across these six categories, should match the expertise of the provider, and should use the available resources in the practice setting. The purpose of this review is combine the findings of a comprehensive review of the published literature with respect to the management of blisters in the partial-thickness burn into a clinical guideline for best practice based on available evidence.

Bandages↗

Basal lamina components in experimentally induced skin blisters.

The distribution of basement membrane glycoproteins, fibronectin, laminin, and type IV collagen was studied in experimentally induced skin blisters in which the epidermis is separated from the dermis through the lamina lucida part of basal lamina. Fibronectin was found surrounding the blister cavity and in a primary covering formed on the bottom of the blister. Neither laminin nor type IV collagen were incorporated into this clot-like matrix. The layer of laminin found in normal epidermal-dermal junction was found to be cleaved by the blistering method, whereas all type IV collagen antigenicity was confined to the base of the blister presumably due to its location in the lamina densa part of the basal lamina. No interstitial collagens were found in the separated epidermis in accordance with previous ultrastructural evidence. These studies support the proposed role of laminin in the adhesion of epidermal cells to basement membrane collagen.

Basement Membrane↗

Biochemical composition of suction blister fluid determined by high resolution multicomponent analysis (capillary gas chromatography--mass spectrometry and two-dimensional electrophoresis).

The biochemical composition of blister fluid was compared with serum and with blister fluid from erythematous lesions induced by ultraviolet irradiation. By using glass capillary gas chromatography--mass spectrometry over 100 metabolites were determined and with the aid of two-dimensional high resolution electrophoresis (the ISO-DALT system) several hundred protein spots were seen. The results show that the suction blister fluid qualitatively have a serum-like pattern but that the concentration of each compound was smaller than in serum. Also in suction blisters raised on erythematous reactions induced by ultraviolet light the same pattern was seen. The content of sodium, potassium and chloride was the same in suction blisters raised on erythematous and normal skin as that of serum.

Blister↗

High levels of hyaluronate in suction blister fluid from active psoriatic lesions.

Hyaluronate concentrations were measured in suction blister fluid from blisters raised on the abdominal skin of 12 healthy control subjects, on unaffected skin of 14 patients with psoriasis, and on lesional skin from 12 of these patients. The concentrations of hyaluronate in blister fluid from the controls and from the uninvolved skin of patients with psoriasis were within the same range (2.9-10.5 and 2.4-7.8 mg/l, respectively). Six of the patients had active, widespread, untreated psoriasis and in these cases the hyaluronate concentration in blister fluid from lesional skin was greatly increased (24-30 mg/l). Patients with stable or regressing psoriasis had no significant increase in hyaluronate levels in the blister fluid from lesional skin compared with the controls (range 4.6-12.4 mg/l). Patients with active psoriasis had significantly higher serum hyaluronate concentrations than the controls and those with inactive psoriasis.

Adult↗

The BB-isoenzyme is a major component of creatine kinase in skin blister fluid.

We measured levels of creatine kinase and its three isoenzymes in serum and blister fluid from 16 healthy volunteers. The BB-isoenzyme was found to be the predominant form in blister fluid while only the MM isoenzyme was found in serum. The levels of BB-isoenzyme in blister fluid decreased as the blisters aged. The source of BB-isoenzyme in blister fluid is most probably the damaged epidermis.

Adult↗

Sulfonamide and trimethoprim concentrations in human serum and skin blister fluid.

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.

Adult↗

Difference in blister fluid penetration after single and multiple doses of ceftriaxone.

Plasma and suction skin blister fluid concentrations of ceftriaxone were studied in 12 subjects after intravenous administration of 1 g of ceftriaxone every 12 h (q12h) and 2 g every 24 h (q24h) after single and multiple doses. Ceftriaxone concentrations were determined by high-pressure liquid chromatography. Mean peak plasma concentrations (at the end of the 5-min infusion) were 254.0 and 374.8 micrograms/ml after administration of 1 g q12h after single and multiple doses, respectively. Similarly, with 2 g q24h, maximum levels were 409.6 and 443.5 micrograms/ml. Forty-eight hours after the last dose of ceftriaxone, plasma concentrations were still detectable: 1.2 micrograms/ml after 1 g q12h and 3.0 micrograms/ml after 2 g q24h. Higher ceftriaxone concentrations were observed in blister fluid after multiple doses than after a single dose. Peak concentrations almost doubled in the blister fluid after multiple doses: 36.0 versus 67.0 micrograms/ml and 38.6 versus 68.9 micrograms/ml for 1 g q12h and 2 g q24h, respectively. Elimination half-life of ceftriaxone in the blister (8.3 and 11.5 h) was longer than plasma half-life (6.3 h). With the area under the concentration-time curve ratio, a 113% increase in tissue penetration was observed after multiple doses for the 1 g q12h regimen. The free plasma and blister fluid ceftriaxone concentrations observed at the end of the dosing interval of the 2 g q24h regimen were higher than the MIC for 90% of the susceptible microorganisms and justified the once-a-day use of ceftriaxone.

Adult↗

Multiple-dose pharmacokinetics of ofloxacin in serum, saliva, and skin blister fluid of healthy volunteers.

The pharmacokinetics of ofloxacin were determined in six healthy volunteers after oral administration of 200 mg twice daily for 3.5 days. To study the pharmacokinetic behavior at the target site in bacterial infection of the skin, drug concentrations were determined in suction blister fluid (SBF) and cantharides blister fluid (CBF), as well as in serum and saliva. Ofloxacin was measured by a high-performance liquid chromatographic assay. Ofloxacin concentrations in saliva amounted to 61 +/- 3% of levels in serum. After the final dose, ofloxacin concentrations in blister fluid and serum declined in parallel. Terminal half-lives of ofloxacin in blister fluids (SBF, 7.0 h; CBF, 6.3 h) were in accordance with serum half-life (6.6 h). Favorable penetration into the skin is suggested by high area under the concentration-time curve ratios for blister fluid and serum (CBF, 1.1; SBF, 1.3). During repeated ofloxacin intake, drug levels in SBF and CBF at 12 h amounted to 0.94 and 1.10 micrograms/ml. Thus, ofloxacin levels in the skin are well above the MIC for 90% of strains tested for, e.g., Staphylococcus aureus, Staphylococcus epidermidis, Neisseria gonorrhoeae, and various members of the family Enterobacteriaceae. This should also hold true with respect to other tissues.

Adult↗

Pharmacokinetic disposition and bactericidal activities of cefepime, ceftazidime, and cefoperazone in serum and blister fluid.

Cefepime is a new broad-spectrum cephalosporin with excellent gram-positive and gram-negative activity including activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Enterobacter cloacae. The pharmacokinetic disposition of cefepime is similar to that of ceftazidime. We compared the pharmacokinetic characteristics and the extent and duration of bactericidal activity in serum and suction-induced blister fluid after single 2-g intravenous doses of cefepime, ceftazidime, and cefoperazone given to healthy subjects. One clinical isolate each of E. cloacae, P. aeruginosa, and S. aureus was used to assess bactericidal activity. Results of the pharmacokinetic analysis were similar to previously reported data for these drugs. The high serum protein binding of cefoperazone (approximately 90%) contributed to poor blister fluid penetration. The other drugs penetrated well into this fluid compartment. Cefepime showed significantly greater bactericidal activity in serum and blister fluid against E. cloacae than the other study drugs, ceftazidime was significantly better in serum and blister fluid against P. aeruginosa, and cefoperazone was significantly better against S. aureus only in serum. None of the study drugs had significant bactericidal activity in blister fluid against S. aureus. Cefepime is a promising antimicrobial agent for the treatment of infections due to E. cloacae.

Adult↗

Penetration of fleroxacin and ciprofloxacin into skin blister fluid: a comparative study.

The penetration of multiple-dose concentrations of oral fleroxacin (400 mg every 24 h) and ciprofloxacin (500 mg every 12 h) into skin blister fluid in 12 healthy volunteers was determined in a randomized crossover study. Serum, blister fluid, and paper disk samples were analyzed by large-plate microbiologic assay. The mean areas under the concentration-time curve (AUC) for serum were 88.6 and 18.2 micrograms.h/ml/70 kg for fleroxacin and ciprofloxacin, respectively. The mean AUC for blister fluid and paper disks were 71.2 and 15.0 micrograms.h/ml/70 kg and 77.8 and 15.4 micrograms.h/ml/70 kg for fleroxacin and ciprofloxacin, respectively. Calculated penetration into interstitial fluid ranged from 74 to 92% for fleroxacin and 56 to 96% for ciprofloxacin; penetration was calculated by using the ratio of maximum drug concentration or AUC in blister fluid and paper disks to maximum drug concentration or AUC in serum. There was no significant difference between fleroxacin and ciprofloxacin in the percent penetration into skin blister fluid.

Administration, Oral↗

Pharmacokinetics of cefetamet in plasma and skin blister fluid.

Cefetamet pivoxil is an oral cephalosporin with enhanced affinity for the target penicillin-binding proteins 1 and 3 and an increased stability to beta-lactamases compared with older cephalosporins, such as cefalexin or cefaclor. The pharmacokinetics of cefetamet pivoxil was determined after the seventh and final dose of 500 mg of cefetamet pivoxil in eight healthy volunteers. Concentrations in plasma and cantharidin-induced skin blister fluid were determined by a high-performance liquid chromatography method. In addition, protein binding was assessed. Cmax was 4.8 +/- 1.7 micrograms/ml in skin blister fluid and 5.1 +/- 2.1 micrograms/ml in plasma. Tmax was delayed in skin blister fluid compared with plasma (3.9 +/- 1 versus 2.8 +/- 0.8 h; P < 0.001), and t1/2 was longer in skin blister fluid than in plasma (3.1 +/- 0.5 versus 2.3 +/- 0.3; P < 0.005). The mean percent penetration into cantharide blister fluid was 129% +/- 24% when measured as total drug and 149% +/- 28% when measured as free drug (P < 0.001). These data suggest that cefetamet has an excellent penetration into inflammatory interstitial fluid.

Adult↗

Tissue penetration by ertapenem, a parenteral carbapenem administered once daily, in suction-induced skin blister fluid in healthy young volunteers.

The penetration of 1 g of intravenous ertapenem once daily for 3 days in suction-induced skin blisters was evaluated. Ten forearm blisters were formed (n = 12) 12 h prior to the last dose. Concentrations of ertapenem in blister fluid exceeded 4 micro g/ml (the MIC at which 90% of the isolates tested are eliminated) for the entire dosing interval. The area under the concentration-time curve for 0 to 24 h ratio of blister fluid to plasma was 61% (90% confidence interval, 56, 65%) suggesting good blister penetration.

Adult↗

Pharmacokinetic profile of meropenem, administered at 500 milligrams every 8 hours, in plasma and cantharidin-induced skin blister fluid.

The pharmacokinetic disposition of meropenem, administered at 500 mg every 8 h, in plasma and cantharidin-induced blister fluid is described. Peak meropenem concentrations in blister fluid lagged behind peak meropenem concentrations in plasma, while a lower elimination rate from blister fluid was also noted. The mean penetration of meropenem into blister fluid was 67%. The pharmacokinetic profile of meropenem in blister fluid supports the utility of this dose in the management of skin and soft tissue infections.

Adult↗