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At least 73 records · Page 4Linked to original sources
PubMed1982

Does cantharides blister fluid provide access to the peripheral compartment?

The pharmacokinetics of bendroflumethiazide (BFT) was investigated following the oral administration of 10 mg to 3 healthy volunteers. Each subject participated twice in the study. BFT was determined in plasma and cantharides blister fluid from 1/2 to 30 h post administration. Blister fluid was obtained from blisters 10-22 h old. Plasma levels were fitted to a tri-exponential equation and the concentration of the drug in the peripheral compartment was calculated from the microscopic rate constants. In 5 of 6 cases investigated, cantharides blister fluid levels paralleled the concentration of the drug in the peripheral compartment. The mean blister fluid levels exceeded the calculated concentration in Compartment 2 1.46 fold. In one case, the blister fluid level paralleled the plasma level. This subject clearly differed from the others as more than 10 h were required for blister formation in her. The results suggest that following the administration of BFT, cantharides blister fluid behaves as part of the peripheral compartment. The possible value of studying blister fluid levels in pharmacokinetic investigations is discussed.

Adult↗
PubMed1983

A local potent glucocorticosteroid decreases the induction of galactosylhydroxylysyl glucosyltransferase in suction blisters but has no effect on basement membrane structures.

The effects of local glucocorticosteroid treatment on collagen biosynthesis and basement membrane components were studied in suction blisters in human abdominal skin. Pretreatment with clobetasol-17-propionate, applied three times a day for 4 days, did not affect the activity of galactosylhydroxylysyl glucosyltransferase (GGT) in fresh blisters but post-blistering treatment for 3 days with the steroid markedly inhibited the increase of this enzyme activity during the initial phases of re-epithelialization. The GGT activity was over 50% lower in steroid-treated blisters compared with control values. Protein concentrations and blister fluid volumes were also significantly decreased in healing 3-day blisters after steroid treatment. These results suggest that local glucocorticosteroid decreases either the synthesis of GGT or its release from the tissue into the blister fluid. The treatment did not affect the blister histology nor the early process of re-epithelialization. Immunohistochemically, type IV and V collagens and laminin of the basement membrane zone were similarly located in blisters of steroid-treated and placebo-treated skin, suggesting that local glucocorticosteroid does not affect the integrity of the basement membrane.

Adult↗
PubMed1994

Correlated increases of tumour necrosis factor-alpha, interleukin-6 and granulocyte monocyte-colony stimulating factor levels in suction blister fluids and sera of psoriatic patients--relationships with disease severity.

Tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and granulocyte monocyte-colony stimulating factor (GM-CSF) were measured in serum and involved and uninvolved skin blister fluids of 20 psoriatic patients and 10 healthy subjects, by enzyme immunoassay. TNF-alpha and IL-6 were always detectable in involved skin blister fluids, while GM-CSF was detected only in 45% of these samples. TNF-alpha, IL-6 and GM-CSF were detected in 95, 100 and 10% of uninvolved skin blister fluid samples, respectively. TNF-alpha and IL-6 were found in 50 and 30% of control blister fluids, while GM-CSF was never detected. In serum, TNF-alpha was detected in 75% of patients and in 70% of controls; IL-6 in 45% of patients and in no controls; and GM-CSF in 35% of patients and in 20% of the controls. The median TNF-alpha and IL-6 levels in involved skin were statistically higher than those of both uninvolved and control skin blister fluids. TNF-alpha and IL-6 levels in blister fluids obtained from both involved and uninvolved skin were higher than those of the patients' sera. GM-CSF, when present in involved skin blister fluids, showed correlated levels with the other cytokines (TNF-alpha: R = 0.85, P = 0.004; IL-6: R = 0.72, P = 0.03). TNF-alpha was highly correlated with IL-6 (R = 0.78, P < 0.00001) in involved skin blister fluids. TNF-alpha and IL-6 levels of involved skin blister fluids showed significant correlations with the psoriasis area and severity index scores in the patients, suggesting a direct relationship between these cytokines and the clinical manifestations of the disease. Moreover, the TNF-alpha levels were particularly related to the erythema scores in the patients, further supporting evidence of their role in the pathogenesis of the disease.

Adolescent↗
PubMed1992

Serum and blister fluid pharmacokinetics and bactericidal activities of ampicillin-sulbactam, cefotetan, cefoxitin, ceftizoxime, and ticarcillin-clavulanate.

Ampicillin-sulbactam, ticarcillin-clavulanate, cefoxitin, cefotetan, and ceftizoxime are promoted for the treatment of mixed aerobic-anaerobic bacterial infections. Their activities have been compared in vitro but not in vivo. In order to assess the in vivo activities of these agents in serum and interstitial fluid, we administered single, intravenous doses of these antimicrobial agents to healthy subjects. Concentrations of the antimicrobial agents in serum and suction-induced blister fluid and bactericidal activity were measured by high-pressure liquid chromatography and the standard methodology of the National Committee for Clinical Laboratory Standards, respectively. The organisms used for bactericidal activity tests were one isolate each of Staphylococcus aureus, Klebsiella pneumoniae, and Bacteroides fragilis. Pharmacokinetic parameters in serum and blister fluid were similar to those derived in other investigations. Of note were the high and prolonged concentrations of ticarcillin and cefotetan in blister fluid, despite high-level serum protein binding. The bactericidal activities in serum and blister fluid reflected the relative in vitro activities and kinetic dispositions of the various antimicrobial agents except for the bactericidal activity of cefotetan, which was substantially lower in blister fluid than serum, despite a blister fluid:serum area under the concentration-time curve ratio of 1.5. Similarly, the activity of ticarcillin-clavulanate in blister fluid was also substantially less than would have been predicted by the blister fluid:serum ratio of the area under the concentration-time curve of 1.1, possibly because of the low concentrations of clavulanate in blister fluid. The rankings of the in vivo bactericidal activities of the five drugs were as follows: for S. aureus, ampicillin-sulbactam > ticarcillin-clavulanate > ceftizoxime > cefoxitin > cefotetan; for K. pneumoniae, ceftizoxime > cefotetan > ampicillin-sulbactam = ticarcillin-clavulanate > cefoxitin; and for B.fragilis, ticarcillin-clavulanate > cefotetan > ceftizoxime > ampicillin-sulbactam = cefoxitin.

Adult↗
PubMed1983

Opsonic activity of blister fluid from burn patients.

The combination of skin loss and immune depression after thermal injury predisposes burn patients to an increased risk of infection. Since the commonest site of infection in the burn patient is the burn wound itself, we elected to study the opsonic activity of locally produced blister fluid, from 18 thermally injured patients, for the two most common organisms colonizing the burn wound (Pseudomonas aeruginosa and Staphylococcus aureus). Blister fluid was as good an opsonin source for staphylococcus as normal serum. In contrast, the blister fluid did not support either the phagocytosis of the intracellular killing of P. aeruginosa. The poor opsonic activity of blister fluid for P. aeruginosa did not appear to be due to the presence of an inhibitory factor(s) since the addition of normal serum restored the opsonic activity of the blister fluid to normal. The concentrations of immunoglobulins and the complement components C3 and C4 in the blister fluid samples were less than half the level of those in normal serum. The opsonic activity of the blister fluid could not be restored to normal by the addition of either immunoglobulin or heat-inactivated serum (56 degrees C for 30 min). Thus, the opsonic factor(s) missing from the blister fluid was heat labile and thus probably represents complement components. That blister fluid had impaired opsonic activity for P. aeruginosa but not for S. aureus indicated that a local humoral defect may be responsible, at least in part, for the high incidence of gram-negative organisms, especially pseudomonads, colonizing the burn wound after thermal injury.

Adolescent↗
PubMedDate not supplied

Differential modulation of transforming growth factor-beta by betamethasone-17- valerate and isotretinoin: corticosteroid decreases and isotretinoin increases the level of transforming growth factor-beta in suction blister fluid.

Retinoids and glucocorticoids are known to have a potential to modulate the expression of transforming growth factor-beta (TGF-beta). We investigated the effect of oral isotretinoin (13-cis-retinoic acid) on the expression of two distinct isoforms of TGF-beta, TGF-beta1 and TGF-beta2, in suction blister fluid and serum in acne patients. We also investigated the effect of topical glucocorticoid (betamethasone-17-valerate) and age on suction blister fluid TGF-beta1 in healthy volunteers. Six weeks of isotretinoin treatment caused a statistically significant 19% increase in suction blister fluid TGF-beta1. The suction blister fluid TGF-beta2 level remained below the sensitivity level of the immunoassay in many cases. Isotretinoin did not affect the serum TGF-beta1 or TGF-beta2 level. Betamethasone-17-valerate pretreatment for 3 days twice a day caused a statistically significant 17% decrease in suction blister fluid TGF-beta1. The active form of TGF-beta1 represented 5% of the total TGF-beta1 in suction blister fluid. Our diffusion calculations suggest that all TGF-beta1 and TGF-beta2 detected in suction blister fluid have diffused from systemic circulation. The increase in suction blister fluid TGF-beta1 after isotretinoin treatment seems to be of local origin, while the decrease in suction blister fluid TGF-beta1 after glucocorticoid pretreatment seems to be due to glucocorticoid-induced vasoconstriction resulting in decreased diffusion of TGF-beta1 from the circulation. Modulation of local interstitial fluid TGF-beta1 concentration may be one mechanism by which isotretinoin and glucocorticoids mediate their effects in skin.

Acne Vulgaris↗
PubMed2003

Tape blisters following hip surgery. A prospective, randomized study of two types of tape.

BACKGROUND: Tape blisters after hip surgery can be a source of postoperative morbidity and can increase patient discomfort. The purpose of this prospective study was to compare two different types of tape to determine whether the type of tape influences the rate of blister formation. METHODS: Ninety-nine patients (100 hips) were enrolled in the study. Patients were randomized into one of two treatment groups: one treated with a nonstretchable silk tape and one treated with a perforated, stretchable cloth tape. After surgery, the assigned tape was applied over the postoperative dressing with care not to produce skin tension. At the first dressing change, the presence or absence of blisters was recorded as were the number, size, location, and type of any blisters. The presence or absence of tape blisters was recorded at the time of each subsequent dressing change. RESULTS: A tape blister developed on twenty-five hips in twenty-five patients. The risk of a blister developing was 41% (twenty of forty-nine patients) when the nonstretchable silk tape was used and 10% (five of fifty patients) when the perforated cloth tape was used (relative risk = 4.08, 95% confidence interval = 1.53 to 10.87, p = 0.005). We found no association between formation of tape blisters and the age or gender of the patient, number of medical comorbidities, smoking history, results of nutritional assessment, or type of surgery. CONCLUSIONS: The prevalence of tape blisters was significantly lower when perforated cloth tape was used than it was when nonstretchable silk tape was used.

Adolescent↗
PubMed1978

The induction of axial blisters in the chick embryo by trypan blue.

The hemorrhage, blister formation, and rumplessness observed in the chick embryo following treatment with trypan blue may be due to (1) increased ventricular blood pressure or (2) to necrosis and edema in the caudal region of the embryo by inhibiting nutrient utilization. To test the role of increased ventricular blood pressure in the induction of caudal blisters, primitive streak to 7-somite chick embryos were cut in half, separating the upper presumptive heart region from the lower presumptive trunk and tail regions. Each half was then explanted on media containing trypan blue for 24 hours. In intact embryos treated with 0.04 mM trypan blue the frequency of blisters in the posterior region was 80.8%. The blisters usually appeared on both sides of the neural tube, below or in the region of the last few somites. In transected embryos treated with trypan blue, the frequency of blisters in the posterior halves which had beating hearts was 2.6%. However, the frequency of blisters in the posterior halves which were not connected to beating hearts was 47.8%. In some cases the blisters were found in posterior halves in which the rump was not well developed or present at all. Thus, we may conclude that: (1) direct connection between the heart and the rump is not necessary for the induction of caudal blisters. (2) The presence of a well-differentiated rump is also not necessary for blister formation. We suggest that trypan blue acts directly on organs or structures found in the caudal region of the chick embryos.

Abnormalities, Drug-Induced↗
PubMed1986

The effect of Goeckerman therapy on interferon in serum and suction blister fluid from patients with psoriasis.

An infectivity inhibition micromethod was used to detect interferon (IFN) in sera and suction blister fluids from 35 patients with untreated psoriasis vulgaris. IFN (greater than or equal to 16 units/ml) was detected in 56% of the sera (median 25 units/ml), in 77% of the suction blister fluids from lesional skin (median 35 units/ml) and 33% of the blister fluids from unaffected skin (median 10 units/ml). IFN levels were significantly higher in blister fluids from lesional skin than from unaffected skin (P less than 0.05) indicating local IFN production. Results of characterization experiments indicated the presence of both acid stable and acid labile IFN-alpha as well as IFN-gamma in sera and blister fluids. After Goeckerman therapy, IFN was detected in 91% of the sera (median 89 units/ml), in 90% of the blister fluids from lesional skin (median 50.5 units/ml) and in 72% of the blister fluids from unaffected skin (median 26.5 units/ml). The IFN levels in sera were significantly higher than in blister fluids from both lesional skin (P = 0.05), and unaffected skin (P = 0.001). Furthermore, after Goeckerman therapy the IFN levels in blister fluids from unaffected skin and in sera were significantly higher than those in untreated patients (P = 0.01 and P = 0.0001) respectively. The results indicate that UVB radiation induces systemic IFN production.

Adolescent↗
PubMedDate not supplied

Reliable site for suction blister induction and harvesting.

BACKGROUND: Suction blister grafting is a useful modality of treatment of patients with resistant and stable vitiligo. However, there have been no detailed studies to find out the best donor site for blister formation. METHODS: The study was conducted between the period of October 2004 and February 2005 in the dermatology department at a tertiary care center. Nine patients with vitiligo (focal vitiligo, 3; mucosal vitiligo, 2; acrofacial vitiligo, 2; vitiligo vulgaris, 1; and segmental vitiligo, 1) were selected for blister harvesting and grafting. The blisters were raised using the method described by Gupta et al. RESULTS: Suction blisters were attempted to be raised at 52 sites, but only 38 blisters could be raised, 24 complete and 14 incomplete. Blisters were raised in all the three cases on the flexor aspect of the arm (100%), 15 of 17 cases (88.2%) on the flexor aspect of the forearm, 4 of 5 cases (80%) on the abdomen, 11 of 16 cases (68.7%) on the anterolateral thigh, and less frequently over leg or foot. Complete blisters were formed in 13/15 cases (86.6%) on the flexor aspect of the forearm, 6/11 cases (54.5%) on the anterolateral thigh, and in all cases over leg. CONCLUSION: The flexor aspect of the forearm is a good site for suction blister harvesting.

Adolescent↗
PubMed2000

End of the century overview of skin blisters.

A wide spectrum of diseases of the skin are manifested as a blistering process. Blistering may occur as a secondary event associated with viral or bacterial infections of the skin, eg, herpes simplex and impetigo, or with local injury of the skin, eg, burns, ischemia, and dermatitis. In other diseases, blistering of the skin occurs as a primary event and is associated with tissue injury and fluid accumulation within a specific layer of the skin: intraepidermal, dermal-epidermal junction, or subepidermal. Blister formation in this latter group of diseases is due to either genetic mutation or an autoimmune response. Genodermatoses associated with blisters are typically manifested in the neonate, whereas the autoimmune blistering disorders are acquired and usually expressed later in life. Recent advances have uncovered the relevance of the keratinocyte cytoskeleton, the desmosome, the hemidesmosome, and extracellular matrix proteins in blister formation. A pathogenetic classification of blistering diseases is presented.

Blister↗
PubMed1991

Peak blistering point: influence on fluid levels of 5-MOP in human skin in vivo after systemic administration.

The concentration of 5-methoxypsoralen (5-MOP) in suction blister fluid (SBF) after oral intake was determined in relation to the peak blistering point. Interstitial fluid was obtained from nine healthy male volunteers by applying mild suction (300-350 mmHg) to the skin of the volar aspect of the forearm. Blisters were raised at three different times: 18 h prior to drug administration (group I); 2 h prior to drug administration (group II); and during drug ingestion (group III). SBF levels of 5-MOP were determined in each group of blisters 2 h after oral administration of 1.2 mg/kg micronized 5-MOP. The results showed a statistically significant difference in the concentrations of 5-MOP between each group of blisters. The highest concentration of 5-MOP in the SBF was found in group III and the lowest in group II blisters. These findings suggest that the point of peak blistering in relation to drug administration needs to be known in each pharmacological study using suction blisters.

5-Methoxypsoralen↗
PubMed1996

Plasma and skin suction-blister-fluid pharmacokinetics and time course of the effects of oral mizolastine.

OBJECTIVE: To investigate plasma and skin suction-blister-fluid pharmacokinetics of oral mizolastine in order to determine whether the drug concentration in the fluid of suction-induced skin blisters could better predict the antihistamine activity than the plasma concentration. SETTING: Department of Internal Medicine, Université Paris 6. SUBJECTS: Ten healthy male volunteers. METHODS: The volunteers (mean age 26.8 years, mean weight 75.8 kg) received a single 10-mg oral dose of mizolastine at 1000 hours. The pharmacokinetic study included 11 plasma and 9 blister fluid samples and blister epidermal-roof specimens. Mizolastine was assayed by high-performance liquid chromatography (HPLC). Each volunteer also received nine intradermal injections of 5 micrograms histamine. Antihistamine activity was assessed as the post-treatment percentages of changes in the histamine-induced relative wheal and flare areas versus baseline. RESULTS: Mizolastine mean Cmax (SD) and median tmax were, respectively, 380 ng.ml-1 and 0.8 h in plasma, and 21.8 ng.ml-1 and 10 h in blister fluid. Mizolastine could not be quantified in the epidermis. The maximal histamine-induced relative flare inhibition was 72.5% and was attained at the median time of 3 h post-dosing and therefore was delayed by 2.2 h with respect to the plasma tmax. Mean relative wheal inhibition, although lower, showed the same time profile. A direct relationship could not be found between drug concentrations in blister fluid and antihistamine activity. Simulated concentrations in the peripheral compartment better explain the maximum inhibition effect on flare, observed 3 h post-dosing, with a flatter hysteresis loop obtained when plotting relative flare inhibition versus plasma or blister-fluid drug concentrations. CONCLUSION: The mizolastine concentrations in the skin suction-blister fluid were not predictive of the antihistamine activity.

Administration, Oral↗
PubMed1996

Detection of IL-1 alpha, IL-1 beta and IL-1 receptor antagonist in blister fluid of bullous pemphigoid.

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease. In addition to autoantibodies, complement activation and inflammatory cells are necessary for lesion formation. In this study, we investigated the potential involvement of IL-1, secreted by various inflammatory and non-inflammatory cells, in BP lesions. We determined IL-1 alpha IL-1 beta and IL-1 receptor antagonist in both blister fluid and concurrent serum samples of 10 BP patients by ELISAs. For comparison, we assayed experimentally generated suction blisters from 10 healthy volunteers. IL-1 beta levels were significantly elevated in BP blisters, whereas levels of IL-1 alpha were decreased relative to those in controls. In concurrent serum samples, no IL-1 alpha or IL-1 beta were detected in patients or controls. Levels of IL-1 receptor antagonist were significantly higher in BP blisters in relation to both concurrent sera and suction blisters. Our data indicate the release of IL-1 beta, IL-1 receptor antagonist, and to a lesser extent, of IL-1 alpha, at the site of blister formation in BP and support the notion that cell-mediated immune mechanisms may contribute to blister formation in this disease.

Aged↗
PubMedDate not supplied

Pharmacokinetics of ampicillin in serum and in dermal suction blisters after oral administration of bacampicillin.

After oral administration of 0.8 g of bacampicillin, the median concentration of ampicillin in serum peaked at 1-2 hr and reached 8.4 and 12.3 micrograms/ml in two groups of 13 and four healthy volunteers, respectively. In the fluid of dermal blisters produced by suction, the peak values were 2.6 and 2.7 micrograms/ml, respectively. After oral administration of 1.6 g of bacampicillin to four healthy individuals, the median peak concentrations were 15.5 micrograms/ml in serum and 3.8 micrograms/ml in blister fluid. The rate of penetration of ampicillin into the blister fluid was lower than the rate of gastrointestinal absorption of bacampicillin, and the elimination of ampicillin from the blister fluid was slower than from serum; the half-life in blister fluid was approximately twice that in serum. Concentrations of ampicillin in the blister fluid exceeded those in serum at greater than or equal to 3 hr. Concentrations of less than 0.7 micrograms/ml were observed in blister fluid 11 hr after administration of the dose. The bioavailability of ampicillin was relatively greater after a 1.6-g dose of bacampicillin than after a 0.8-g dose. Inflammation in the blister fluid that was induced by endotoxin, which provoked a strong cellular response but cased no increase in the concentration of protein in the fluid, did not significantly influence the pharmacokinetics of ampicillin. The results suggest that the pharmacokinetics of antimicrobial agents in serum and in extravascular foci may be relevant to the setting of breakpoints between sensitivity and resistance of pathogens of antimicrobial agents.

Administration, Oral↗
PubMed2005

Production of lysophosphatidic acid in blister fluid: involvement of a lysophospholipase D activity.

Lysophosphatidic acid (LPA) is present in abundance in serum resulting from platelet activation and is also found in other biological fluids. LPA controls numerous cellular responses and plays a role in specific functions such as wound healing, especially in the skin. Nevertheless, its presence in the skin has never been investigated. Since re-epithelialization occurs after blister rupture, we tested the presence of endogenous LPA in blister fluid and investigated a possible mechanism for its biosynthesis and biological functions. Using a radioenzymatic assay, LPA was detected in 33 blister fluids originating from 24 bullous dermatoses, and at higher concentrations than in plasma. In parallel, blister fluids contained a lysophospholipase D (LPLD) activity but no detectable phospholipase A2 activity. The expressions of the LPLD autotaxin (ATX) and of LPA1-receptor (LPA1-R) were greatly increased in blister skin when compared with normal skin. Finally, LPA was found to have a positive effect on the migration of cultured keratinocytes. These results show that LPA is present in blister fluid synthesized by the LPLD ATX. Due to its ability to enhance keratinocyte migration, LPA in blister fluid could, via the LPA1-R, play an important role in re-epithelialization occurring after blister rupture.

Adult↗
PubMed1989

The localization of the bullous pemphigoid and cicatricial pemphigoid antigens: direct and indirect immunofluorescence of suction blisters.

The location of in vivo bound immunoreactants was studied in 37 patients with subepidermal blistering diseases by direct immunofluorescence (IMF) on suction blisters taken from uninvolved forearm skin. The patients studied included 18 with bullous pemphigoid (BP), nine with cicatricial pemphigoid (CP), three with acquired epidermolysis bullosa (EBA) and 7 hybrid cases. The patterns of IMF in the suction blisters were: BP, epidermal 1, dermal 1, combined 4, negative 12; CP, epidermal 1, dermal 2, negative 6; EBA, dermal 2, negative 1; and 'hybrid' patients, epidermal 3, negative 4. The different patterns of suction blister staining could not be correlated with the clinical features of the patients in respect of mucous membrane involvement, scars or milia or a history of skin fragility. Both BP and CP are probably heterogeneous in respect of their antigen specificity, and the two diseases cannot reliably be distinguished by the patterns of direct IMF on suction blisters. In addition, some individual patients with BP have more than one target antigen as indicated by a combined pattern of suction blister fluorescence. The lack of correlation between the pattern of suction blister fluorescence and the clinical features suggests that factors other than antigen specificity determine the clinical expression of subepidermal blistering diseases.

Adult↗
PubMed2005

Pharmacokinetics of oritavancin in plasma and skin blister fluid following administration of a 200-milligram dose for 3 days or a single 800-milligram dose.

Oritavancin is a novel glycopeptide currently being developed for the treatment of complicated skin and skin structure infections (cSSSI), including those caused by multidrug resistant gram-positive pathogens. The disposition of oritavancin in skin structures was investigated using a cantharide-induced blister fluid model. Seventeen healthy male subjects received oritavancin, but only 16 subjects were evaluated after one subject discontinued study drug. Each subject (eight per dose group) received 200 mg of oritavancin once a day for 3 days (group A) or 800 mg as one single dose (group B). Group A plasma samples and exudates from blister fluid were collected on days 3, 4, 7, 9, and 12 and on days 3, 4, 7, and 9, respectively. Group B samples and exudates were collected on days 1, 2, 5, 7, and 10 and on days 1, 2, 5, and 7, respectively. Drug concentrations were determined using a liquid chromatography-tandem mass spectrometry assay and, subsequently, pharmacokinetic analysis was performed. Differences between treatment groups in ratios for area under the concentration-time curve for blister fluid and plasma (AUC(blister fluid)/AUC(plasma) ratios) were evaluated using a t test (alpha = 0.05). Mean maximum concentration of drug in plasma or blister fluid was approximately 8-fold and 11-fold higher in plasma than in blister fluid following the 200- or 800-mg doses of oritavancin, respectively. Mean AUC(blister fluid)/AUC(plasma) ratios at 24 h were 0.190 (standard deviation [SD], 0.052) and 0.182 (SD, 0.062) for groups A and B, respectively (P = 0.791). To place these results in a clinical context, mean drug concentrations in blister fluid exceed the oritavancin MIC at which 90% of strains are inhibited of Staphylococcus aureus (2 microg/ml) by approximately 2- to 5.5-fold at 12 h and 1.5- to 3-fold at 24 h following administration of both dosing regimens. These results support the potential use of oritavancin for the treatment of cSSSI.

Adult↗