Dermo-Epidermal Separation with Suction

We report the results obtained in a comparative study on the extravascular passage of cefotaxime, employing three different methods: suction skin blister, skin window, and skin chamber. Applying the skin blister method in two different ways, we also studied the influence that suction pressure and time lapse between blister formation and antibiotic injection had on the results obtained in order to standardize the method and establish repeatability of the results. Using the skin chamber method, we studied the influence that the different protein contents in the fluid used to fill the skin chamber had on extravascular concentrations.The study of interstitial extravascular passage of antibiotics in humans is an interesting problem which presents considerable limitations because of the lack of material available on dosage systems for the antibiotics. In fact, it is almost impossible to obtain sufficient quantities of the interstitial fluid to make such determining possible.Studies on the extravascular passage of antibiotics in humans have been made, using the skin window (7) and skin chamber methods (10) and more recently, the skin blister method (8).From the published results of studies on this subject, the great diversity of interstitial concentrations of the same antibiotic and the kinetic difference in relation to the methods being used are evident. We found, furthermore, that this difference may be related to diverse characteristics, mainly the different protein contents of the exudates obtained by different methods (R. F. Frongillo, Relazione XX Congresso Nazionale Societa Italiana Malattie Infettive e Parass., in press). It is, therefore, clear that none of the applied methods can produce liquids comparable to the interstitial fluid, since they are, for the most part, exudates or only apparent transudates.The first problem, therefore, is to establish a method which can be standardized easily and which by assuring reproducible results makes feasible a comparative study of the influence of various factors on the extravascular passage of the antibiotics.In recent in vivo and in vitro experiments, using the new cephalosporin cefotaxime, we studied the extravascular concentrations of this antibiotic and compared the results obtained by application of the skin window and skin chamber 22 methods with those obtained by using a suction skin blister method (6). MATERIALS AND METHODSSubjects. Patients 18 to 69 years of age (average age, 56), weighing 42 to 70 kg (average weight, 58 kg), were studied in the Infectious Diseases Institute of the University of Perugia, Italy.No clinical or biochemical alterations in kidney and liver functions were found on examining the patients, who had given their consent for the experiment.Cefotaxime. Cefotaxime (HR 756; Hoechst A. G., Frankfurt, Germany), in 1-g vials diluted in 1% lidocaine for intramuscular injection, was used. Blood and extravascular fluid samples were taken 30 min and 1, 2, and 4 h after the injection.Filter paper disks used in the skin window method were applied imm...

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“…When the fluids were compared in this way, the difference (143.2 [±23] % versus 79. 6 [±46]%) was highly significant (P < 0.01).…”

Section: Methodsmentioning

confidence: 76%

“…In recent in vivo and in vitro experiments, using the new cephalosporin cefotaxime, we studied the extravascular concentrations of this antibiotic and compared the results obtained by application of the skin window and skin chamber 22 methods with those obtained by using a suction skin blister method (6).…”

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confidence: 99%

Suction skin blister, skin window, and skin chamber techniques to determine extravascular passage of cefotaxime in humans

Frongillo¹,

Galuppo²,

Moretti³

1981

Antimicrob Agents Chemother

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“…The epidermis has been found to regenerate rapidly after such sampling, local effects are subclinical, and no invasive complications have been reported [6,19] . The epidermal split occurs reproducibly in the lamina lucida, a structurally weak layer just beneath the basal epidermal cells [20,21] , leaving the lamina densa of the basal lamina as a fi brous cover on the dermis [21,22] . Except for occasional breaks in the most superfi cial dermal capillary loops, the dermis remains intact.…”

Section: Discussionmentioning

confidence: 99%

Transdermal Suctioning Technique for Serial Sampling of Interstitial Fluid in Newborn Infants

Hansen‐Pupp

Håkansson²,

Polberger³

et al. 2005

Neonatology

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Overview: Use of a suction-induced epidermal mini-erosion for serial sampling of dermal interstitial fluid (IF) in 16 newborn infants with gestational age ranging from 24 to 42 weeks is reported. Results: The mini-erosion formed reproducibly and electron microscopy showed that the split was located within the epidermis. IF was sampled serially by suctioning during 1–3 days without signs of stress or pain. IF sample volumes (10–50 µl) did not decrease with time. Glucose values in IF and blood were correlated (r_s = 0.542; p = 0.000). IF glucose was lower than blood glucose on all 3 days. The epidermis regenerated within 4 ± 0.9 days (mean, SD) after sampling was terminated. There were no complications. Conclusion: Serial transdermal sampling was performed without stress or pain in newborn infants. Systemic and temporal differences between glucose measured in IF and blood were observed.

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“…As the suction blister offers an accessible extravascular site Concentration-response relationship [5,6], this model might prove to be useful to investigate concentration-response relationships of antiinflammatory For inhibition of platelet-derived TXB 2 after administration of S-flurbiprofen, a sigmoidal log-linear concentrationdrugs at their site of action in humans. Induction of suction blister has been reported to be a non-inflammatory event response relationship could be established in all volunteers with coefficients of variation for the individual fits ranging [22] on the basis of the lack of cellular infiltration in the early time-frame (up to 24 h) following blister induction. from 0.97 to 17% and correlation coefficients greater than 0.97 in all subjects (Figure 3).…”

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confidence: 99%

Disposition and effects of flurbiprofen enantiomers in human serum and blister fluid

Oelkers

Neupert

Williams

et al. 1997

Brit J Clinical Pharma

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Aims To investigate the pharmacokinetics of the enantiomers of flurbiprofen and inhibition of prostanoid production in blister fluid and serum. Methods Eleven healthy volunteers received 75 mg R-, 75 mg S-flurbiprofen or no medication in a randomized 3-way cross-over study. Flurbiprofen concentrations were determined by h.p.l.c. TXB 2 and PGE 2 were determined by enzyme immunoassay and chemiluminescence immunoassay respectively. Results S-flurbiprofen produced almost complete (>99% vs baseline) inhibition of thromboxane B 2 (TXB 2 ) in serum in all volunteers and significant inhibition of prostaglandin E 2 (PGE 2 ) generation in blister fluid, but there was a considerable inter-individual variation in the response ranging from −78 to +190% change from control PGE 2 AUC. After administration of R-flurbiprofen, there was a mean maximum TXB 2 inhibition of 65.2±15.0% in serum but no significant changes of PGE 2 levels in blister fluid were observed. The pharmacokinetic parameters in serum and blister fluid were not significantly different between enantiomers. R-to S-inversion did not occur to a clinically relevant extent. For R-flurbiprofen, the complex rate constant of transfer into blister fluid was greater at the u.v.-exposed site (0.110±0.050) than at the control site (0.079±0.026, P<0.05) which corresponded to a higher AUC and C max of R-flurbiprofen in u.v.-exposed blister as compared with control. For inhibition of TXB 2 generation after administration of S-flurbiprofen, a sigmoidal log-linear concentration-response relationship was established in all subjects (EC 50 : 0.123±0.092 mg ml −1 ). In contrast, inhibition of PGE 2 production in blister showed no clear concentration-response relationship when correlated with concentrations of S-flurbiprofen in either serum or blister fluid. After administration of R-flurbiprofen, no concentration-effect relationship could be established. Conclusions It is concluded that the blister model may have value for studying the pharmacokinetics and pharmacodynamics of antiinflammatory drugs in humans. Interestingly, inter-individual variation in the pharmacokinetics of flurbiprofen enantiomers could not account for the variability in response observed in the blister model.

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Dermo-Epidermal Separation with Suction

Cited by 231 publications

References 13 publications

Suction skin blister, skin window, and skin chamber techniques to determine extravascular passage of cefotaxime in humans

Suction skin blister, skin window, and skin chamber techniques to determine extravascular passage of cefotaxime in humans

Transdermal Suctioning Technique for Serial Sampling of Interstitial Fluid in Newborn Infants

Disposition and effects of flurbiprofen enantiomers in human serum and blister fluid

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