The Experts below are selected from a list of 546 Experts worldwide ranked by ideXlab platform
Ryan M Pelis - One of the best experts on this subject based on the ideXlab platform.
-
2012. Expression of organic anion transporter 2 in the human kidney and its potential role in the tubular secretion of guanine-containing antiviral drugs. Drug Metab. Dispos
2020Co-Authors: Yaofeng Cheng, Arpine Vapurcuyan, Mohammad Shahidullah, Lauren M Aleksunes, Ryan M PelisAbstract:ABSTRACT: The organic anion transporters 1 and 3 (OAT1 and OAT3) and organic cation transporter 2 (OCT2) are important for renal tubular drug secretion. In contrast, evidence for OAT2 expression in the human kidney is limited, and its role in renal drug transport is unknown. Both mRNA (real-time polymerase chain reaction) and protein (Western blotting) for OAT2 were detected in renal cortex from eight donors, and interindividual variability in protein levels was 3-fold. OAT2 protein in the renal cortex was localized (by immunohistochemistry) to the basolateral domain of tubules, as were OAT1 and OAT3. The absolute abundance of OAT2 mRNA was similar to that of OAT1 mRNA and 3-fold higher than that of OCT2 mRNA but 10-fold lower than that of OAT3 mRNA. A previous observation that OAT2 transports cGMP led us to examine whether acyclovir, ganciclovir, and Penciclovir are OAT2 substrates; they are guanine-containing antivirals that undergo active tubular secretion. Transport of the antivirals into human embryonic kidney cells was stimulated 10-to 20-fold by expression of OAT2, but there was little to no transport of the antivirals by OAT1, OAT3, or OCT2. The K m values for acyclovir, ganciclovir, and Penciclovir transport were 94, 264, and 277 M, respectively, and transport efficiencies were relatively high (6-24 l ⅐ min ؊1 ⅐ mg protein ؊1 ). This study provides definitive evidence for the expression of OAT2 in the human kidney and is the first to demonstrate that OAT2, compared with OAT1, OAT3, or OCT2, has a preference for antiviral drugs mainly eliminated in the urine via active secretion
-
2012. Expression of organic anion transporter 2 in the human kidney and its potential role in the tubular secretion of guanine-containing antiviral drugs. Drug Metab. Dispos
2020Co-Authors: Yaofeng Cheng, Arpine Vapurcuyan, Mohammad Shahidullah, Lauren M Aleksunes, Ryan M PelisAbstract:Abstract The organic anion transporters 1 and 3 (OAT1 and OAT3), and organic cation transporter 2 (OCT2) are important for renal tubular drug secretion. In contrast, evidence for OAT2 expression in the human kidney is limited, and its role in renal drug transport is unknown. Both mRNA (real-time polymerase chain reaction) and protein (Western blotting) for OAT2 was detected in renal cortex from eight donors, and interindividual variability in protein levels was 3-fold. OAT2 protein in the renal cortex was localized (by immunohistochemistry) to the basolateral domain of tubules, as were OAT1 and OAT3. The absolute abundance of OAT2 mRNA was similar to OAT1 mRNA, 3-fold higher than OCT2 mRNA, but 10-fold lower than OAT3 mRNA. A previous observation that OAT2 transports cyclic guanosine monophosphate (cGMP) led us to examine if acyclovir, ganciclovir and Penciclovir are OAT2 substrates; they are guanine-containing antivirals that undergo active tubular secretion. Transport of the antivirals into human embryonic kidney cells was stimulated 10-to 20-fold by expression of OAT2, but there was little to no transport of the antivirals by OAT1, OAT3 or OCT2. The K m values for acyclovir, ganciclovir and Penciclovir transport were 94 µM, 264 µM and 277 µM, respectively, and transport efficiencies were relatively high (6 to 24 µl·min -1 ·mg protein -1 ). This study provides definitive evidence for the expression of OAT2 in the human kidney, and is the first to demonstrate that OAT2, compared to OAT1, OAT3 or OCT2, has a preference for antiviral drugs mainly eliminated in the urine via active secretion
-
Organic anion transporter 2 transcript variant 1 shows broad ligand selectivity when expressed in multiple cell lines
Frontiers Media S.A., 2015Co-Authors: Adam G Hotchkiss, Liam Eberrigan, Ryan M PelisAbstract:Organic anion transporter 2 (OAT2) is likely important for renal and hepatic drug elimination. Three variants of the OAT2 peptide sequence have been described – OAT2 transcript variant 1 (OAT2-tv1), OAT2 transcript variant 2 (OAT2-tv2) and OAT2 transcript variant 3 (OAT2-tv3). Early studies helping to define the ligand selectivity of OAT2 failed to identify the variant used, and the studies used several heterologous expression systems. In preliminary studies using OAT2-tv1, we failed to observe transport of several previously identified substrates, leading us to speculate that ligand selectivity of OAT2 differs with variant and/or heterologous expression system. The purpose was to further investigate the ligand selectivity of the OAT2 variants expressed in multiple cell types. We cloned OAT2-tv1 and OAT2-tv2, but were unsuccessful at amplifying mRNA for OAT2-tv3 from human kidney. OAT2-tv1 and OAT2-tv2 were individually expressed in human embryonic kidney (HEK), Madin-Darby Canine Kidney (MDCK) or Chinese hamster ovary (CHO) cells. mRNA for OAT2-tv1 and OAT2-tv2 was demonstrated in each cell type transfected with the respective construct, indicating their expression. OAT2-tv1 trafficked to the plasma membrane of all three cell types, but OAT2-tv2 did not. OAT2-tv1 transported Penciclovir in all three cell types, but failed to transport para-aminohippurate, succinate, glutarate, estrone-3-sulfate, paclitaxel or dehydroepiandrosterone sulfate – previously identified substrates of OAT2-tv2. Not surprising given its lack of plasma membrane expression, OAT2-tv2 failed to transport any of the organic solutes examined, including Penciclovir. Penciclovir transport by OAT2-tv1 was sensitive to large (e.g., cyclosporine A) and small (e.g., allopurinol) organic compounds, as well as organic anions, cations and neutral compounds, highlighting the multiselectivity of OAT2-tv1. The potencies with which indomethacin, furosemide, cyclosporine A and cimetidine inhibited OAT2-tv1 are in good agreement with previous studies using this variant, but inconsistent with studies using OAT2 with an unidentified sequence. This study shows that organic molecules with diverse physicochemical properties interact with OAT2-tv1, making it a likely site of drug interactions. Many previously identified substrates of OAT2 are not transported by OAT2-tv1, suggesting that variant and/or expression system may contribute. Future work should establish the expression pattern and ligand selectivity of OAT2-tv3
-
expression of organic anion transporter 2 in the human kidney and its potential role in the tubular secretion of guanine containing antiviral drugs
Drug Metabolism and Disposition, 2012Co-Authors: Yaofeng Cheng, Arpine Vapurcuyan, Mohammad Shahidullah, Lauren M Aleksunes, Ryan M PelisAbstract:The organic anion transporters 1 and 3 (OAT1 and OAT3) and organic cation transporter 2 (OCT2) are important for renal tubular drug secretion. In contrast, evidence for OAT2 expression in the human kidney is limited, and its role in renal drug transport is unknown. Both mRNA (real-time polymerase chain reaction) and protein (Western blotting) for OAT2 were detected in renal cortex from eight donors, and interindividual variability in protein levels was 3-fold. OAT2 protein in the renal cortex was localized (by immunohistochemistry) to the basolateral domain of tubules, as were OAT1 and OAT3. The absolute abundance of OAT2 mRNA was similar to that of OAT1 mRNA and 3-fold higher than that of OCT2 mRNA but 10-fold lower than that of OAT3 mRNA. A previous observation that OAT2 transports cGMP led us to examine whether acyclovir, ganciclovir, and Penciclovir are OAT2 substrates; they are guanine-containing antivirals that undergo active tubular secretion. Transport of the antivirals into human embryonic kidney cells was stimulated 10- to 20-fold by expression of OAT2, but there was little to no transport of the antivirals by OAT1, OAT3, or OCT2. The K m values for acyclovir, ganciclovir, and Penciclovir transport were 94, 264, and 277 μM, respectively, and transport efficiencies were relatively high (6–24 μl · min−1 · mg protein−1). This study provides definitive evidence for the expression of OAT2 in the human kidney and is the first to demonstrate that OAT2, compared with OAT1, OAT3, or OCT2, has a preference for antiviral drugs mainly eliminated in the urine via active secretion.
-
and Its Potential Role in the Tubular Secretion of Guanine-Containing Antiviral Drugs
2011Co-Authors: Yaofeng Cheng, Arpine Vapurcuyan, Mohammad Shahidullah, Lauren M Aleksunes, Ryan M PelisAbstract:The organic anion transporters 1 and 3 (OAT1 and OAT3) and organic cation transporter 2 (OCT2) are important for renal tubular drug secretion. In contrast, evidence for OAT2 expression in the human kidney is limited, and its role in renal drug transport is unknown. Both mRNA (real-time polymerase chain reaction) and protein (Western blotting) for OAT2 were detected in renal cortex from eight donors, and interindividual variability in protein levels was 3-fold. OAT2 protein in the renal cortex was localized (by immunohistochemistry) to the basolateral domain of tubules, as were OAT1 and OAT3. The absolute abundance of OAT2 mRNA was similar to that of OAT1 mRNA and 3-fold higher than that of OCT2 mRNA but 10-fold lower than that of OAT3 mRNA. A previous observation that OAT2 transports cGMP led us to examine whether acyclovir, ganciclovir, and Penciclovir are OAT2 substrates; they are guanine-containing antivirals that undergo active tubular se-cretion. Transport of the antivirals into human embryonic kidney cells was stimulated 10- to 20-fold by expression of OAT2, but there was little to no transport of the antivirals by OAT1, OAT3, or OCT2. The Km values for acyclovir, ganciclovir, and Penciclovir transport were 94, 264, and 277 M, respectively, and transport efficiencies were relatively high (6–24 l min1 mg protein1). This study provides definitive evidence for the expression of OAT2 in the human kidney and is the first to demonstrate that OAT2, compared with OAT1, OAT3, or OCT2, has a preference for antiviral drugs mainly eliminated in the urine via active secretion
Stephen Locarnini - One of the best experts on this subject based on the ideXlab platform.
-
preclinical aspects of lamivudine and famciclovir against hepatitis b virus
Journal of Viral Hepatitis, 1999Co-Authors: T Shaw, Stephen LocarniniAbstract:: Chemotherapy for chronic hepatitis B virus (HBV) infection is inherently difficult for a variety of reasons that are related to unusual features of both HBV replication strategy and host cell metabolism. Previous attempts to treat chronic HBV infection using nucleoside analogues have been almost universally disappointing, but several recently developed nucleoside analogues have been identified as potent, non-toxic inhibitors of HBV replication. These fall into two broad categories: nucleosides having the 'unnatural' L-configuration, and deoxyguanosine analogues with modified-sugar configurations, represented by lamivudine and Penciclovir respectively. Both lamivudine and Penciclovir (in its orally available form, famciclovir) have progressed to phase III clinical trials against chronic HBV infection, with promising preliminary results. However, chemotherapy for chronic HBV is necessarily long term, which increases the risks for development of viral resistance and cumulative toxicity. Such risks might be minimized by the use of appropriate drug combinations, rational selection of which requires knowledge of the pharmacokinetics and mechanisms of action of the individual agents. An appreciation of cellular deoxynucleoside metabolism and its regulation, the complexities of which are still emerging, is an indispensable aid to understanding the biological activities of deoxynucleoside analogues. The modes of action of lamividine and Penciclovir, and how these two deoxynucleoside analogues may interact in vitro and in vivo as inhibitors of HBV replication, are examined here in the context of cellular deoxynucleoside metabolism.
-
clinical experience with famciclovir against hepatitis b virus
Intervirology, 1997Co-Authors: Angeline Bartholomeusz, Leo C Groenen, Stephen LocarniniAbstract:Famciclovir (FCV, the oral form of Penciclovir, PCV) is a potent antiviral agent of hepatitis B virus (HBV) and is currently in phase III clinical trials. In this review, we examine the outcome of FCV treatment in preventing recurrent HBV in patients post transplantation. Resistance to FCV has now been documented in this setting, in which reduced sensitivity to FCV was associated with mutations upstream from the conserved ‘YMDD’ motif in the HBV polymerase gene. These mutations are in a region which has been designated as the B domain in RNA-dependent polymerases. To understand these mutations we have developed a model of the catalytic regions of the HBV polymerase and located mutations selected during antiviral treatment on this model.
-
the guanine nucleoside analog Penciclovir is active against chronic duck hepatitis b virus infection in vivo
Antimicrobial Agents and Chemotherapy, 1996Co-Authors: E Lin, Tim Shaw, Carolyn Luscombe, Yanyan Wang, Stephen LocarniniAbstract:Ducks congenitally infected with duck hepatitis B virus (HBV) were treated with the antiviral guanine nucleoside analog Penciclovir for 4 weeks at a dose of 10 mg/kg of body weight per day. The effects of treatment on viremia and intrahepatic viral genome replication, transcription, and translation were examined. In seven of eight Penciclovir-treated ducks, viremia was barely detectable after a week of treatment. After 4 weeks of treatment, molecular hybridization studies showed that intrahepatic viral DNA, RNA, and protein levels were significantly reduced compared with those in placebo-treated controls. Synthesis of all viral replicative intermediates, including the normally persistent viral supercoiled DNA species, was inhibited by Penciclovir treatment. Examination of liver tissue sections after in situ DNA hybridization or immunohistochemical staining confirmed that viral DNA and protein synthesis had been profoundly inhibited in most hepatic parenchymal cells. However, small subpopulations of cells, in particular the small bile duct epithelial cells, remained strongly positive for duck HBV antigens and DNA despite treatment. There was no evidence of toxicity associated with Penciclovir therapy. This study confirms the safety and potent antihepadnaviral activity of Penciclovir in vivo but indicates that further improvements in antiviral therapy will be required to completely eliminate HBV infection.
-
in vitro antiviral activity of Penciclovir a novel purine nucleoside against duck hepatitis b virus
Antimicrobial Agents and Chemotherapy, 1994Co-Authors: Tim Shaw, P Amor, Gilda Civitico, M Boyd, Stephen LocarniniAbstract:The in vitro antihepadnavirus activities of the purine nucleoside analogs ganciclovir (9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine) and Penciclovir [9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine; BRL 39123] were compared in primary duck hepatocyte cultures congenitally infected with the duck hepatitis B virus (DHBV). Both compounds inhibited DHBV DNA replication to a comparable extent during continuous short-term treatment of the cultures. However Penciclovir was more active both during longer-term continuous treatment (50% inhibitory concentrations: Penciclovir, 0.7 +/- 0.1 microM; ganciclovir, 4.0 +/- 0.2 microM) and in washout experiments (50% inhibitory concentrations: Penciclovir, 3.0 +/- 0.4 microM; ganciclovir, 46 +/- 1.5 microM) designed to compare the persistence of inhibitory activity after removal of the extracellular compound. The effects on viral protein synthesis were similar to the effects on viral DNA replication. These data suggest that Penciclovir or its oral form, famciclovir, may have clinical utility in the treatment of chronic hepatitis B virus infection.
Sanjiv S Gambhir - One of the best experts on this subject based on the ideXlab platform.
-
comparison of 14c fmau 3h feau 14c fiau and 3h pcv for monitoring reporter gene expression of wild type and mutant herpes simplex virus type 1 thymidine kinase in cell culture
Molecular Imaging and Biology, 2005Co-Authors: Keon Wook Kang, Jungjoon Min, Xiaoyuan Chen, Sanjiv S GambhirAbstract:Purpose To assess the optimal reporter probe/reporter gene combination for monitoring herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene expression, we compared the cellular uptake of 1-(2′-fluoro-2′-deoxy-d-arabinofuranosyl)-5-methyluracil (FMAU), 2′-fluoro-2′-deoxyarabinofuranosyl-5-ethyluracil (FEAU), 2′-fluoro-2′-deoxy-β-d-arabinofuranosyl-5-iodouracil (FIAU) and Penciclovir (PCV) in both HSV1-tk and HSV1-sr39tk expressing cells.
-
cl1 sr39 a noninvasive molecular imaging model of prostate cancer suicide gene therapy using positron emission tomography
The Journal of Urology, 2002Co-Authors: Allan J Pantuck, Sanjiv S Gambhir, Frank Berger, Amnon Zisman, David Nguyen, Cho Lea Tso, Jamie Matherly, Arie S BelldegrunAbstract:ABSTRACTPurpose: We developed a prostate cancer tumor model capable of being noninvasively imaged using positron emission tomography (PET) based on expression of the herpes simplex virus thymidine kinase (HSV1-tk) reporter gene.Materials and Methods: The androgen independent, metastatic prostate cancer cell lines CL1 and CL1-GFP were stably transfected with the mutant HSV1-tk gene pcDNA3.1/pCMV-sr39tk, which has increased ability to phosphorylate Penciclovir. The presence of the sr39tk gene product was analyzed by Western blot analysis and relative thymidine kinase enzyme activity was assessed by a functional thymidine kinase enzyme activity assay. Subcutaneous and orthotopic CL1 and CL1-SR39 tumor xenografts were established in SCID mice. The ability to image CL1-SR39 was assessed using fluorodeoxyglucose and 18F-Penciclovir (18F-FHBG) micro-PET (a rodent PET scanner). To investigate the systemic distribution of intratumoral sr39tk injections established CL1 tumors were transiently injected with first ge...
Teresa H Bacon - One of the best experts on this subject based on the ideXlab platform.
-
herpes simplex virus resistance to acyclovir and Penciclovir after two decades of antiviral therapy
Clinical Microbiology Reviews, 2003Co-Authors: Teresa H Bacon, Myron J Levin, Jeffry J Leary, Robert T Sarisky, David SuttonAbstract:Acyclovir, Penciclovir, and their prodrugs have been widely used during the past two decades for the treatment of herpesvirus infections. In spite of the distribution of over 2.3 × 10 6 kg of these nucleoside analogues, the prevalence of acyclovir resistance in herpes simplex virus isolates from immunocompetent hosts has remained stable at approximately 0.3%. In immuncompromised patients, in whom the risk for developing resistance is much greater, the prevalence of resistant virus has also remained stable but at a higher level, typically 4 to 7%. These observations are examined in the light of characteristics of the virus, the drugs, and host factors.
-
comparison of a dna probe assay with the plaque reduction assay for measuring the sensitivity of herpes simplex virus and varicella zoster virus to Penciclovir and acyclovir
Journal of Virological Methods, 1996Co-Authors: Ruth Standringcox, Teresa H Bacon, Barbara A HowardAbstract:A DNA probe assay was compared with the plaque reduction assay to determine the sensitivity of clinical isolates of herpes simplex virus (HSV) and varicella-zoster virus (VZV) to Penciclovir and acyclovir in MRC-5 cells. In both assays, Penciclovir and acyclovir shared comparable activity against cell-free virus (CFV) preparations of VZV and herpes simplex virus type 1 (HSV-1) isolates, whilst acyclovir was significantly more active than Penciclovir against herpes simplex virus type 2 (HSV-2) isolates in both the DNA probe assay (P < or = 0.01) and the plaque reduction assay (P < or = 0.01). However, the 50% effective concentrations (EC50s) were generally lower in the DNA probe assay and the correlation between the plaque reduction and DNA probe assays was poor for either compound. Six acyclovir-resistant strains of HSV-1 derived in cell culture were also tested for susceptibility to Penciclovir and acyclovir, in the DNA probe and plaque reduction assays. The relative susceptibilities of these strains were comparable, for example, one ACV-resistant strain was susceptible to Penciclovir in both assays. Further comparisons of the assay methods were made using cell-associated VZV (CAV). As with CFV the EC50s were significantly lower in the DNA probe assay than the plaque reduction assay for Penciclovir (P < or = 0.01) and acyclovir (P < or = 0.01). In the DNA probe assay there was no significant difference in the EC50s for either Penciclovir or acyclovir when comparing CAV with CFV. However, in the plaque reduction assay the EC50s for CAV were significantly higher than those for CFV for both Penciclovir (P < or = 0.01) and acyclovir (P < or = 0.01). Overall the DNA probe assay is objective, does not require prior titration of isolates and provides opportunities for automation. It is more suitable for sensitivity testing of large numbers of clinical isolates than the well-established plaque reduction assay.
-
Mode of antiviral action of Penciclovir in MRC-5 cells infected with herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus. Antimicrob. Agents Chemother
1992Co-Authors: David L. Earnshaw, Teresa H Bacon, Sarah J. Darlison, Kay Edmonds, Robert M. Perkins, Anthony Vere R. Hodge, Smithkline Beecham Pharmaceuticals, Great Burgh, Yew Tree, Bottom RoadAbstract:The metabolism and mode of action of Penciclovir [9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine; BRL 39123] were studied and compared with those of acyclovir. In uninfected MRC-5 cells, low concentrations of the triphosphates of Penciclovir and acyclovir were occasionally just detectable, the limit of detection being about 1 pmol/l0 cells. In contrast, in cells infected with either herpes simplex virus type 2 (HSV-2) or varicella-zoster virus (VZV), Penciclovir was phosphorylated quickly to give high concentrations of the triphosphate ester. Following the removal of Penciclovir from the culture medium, Penciclovir-triphosphate remained traPpd within the cells for a g time hlf-lives, 20 ad 7-h in HSV-2- and VZV-infected cels, respectively). In HSV-2-infected cells, acyclovir was phosphorylated to a lesser extent and the half-life of the triphosphate ester was only 1 h. We were unable to detect any phosphates of acyclovir in VZV-infected cells. (S)-Penciclovir-triphosphate inhibited HSV-1 and HSV-2 DNA polymerases competitively with dGTP, the Ki values being 8.5 and 5.8 FM, respectively, whereas for acyclovir-triphosphate, the 1I value was 0.07,uM for the two enzymes. Both compounds had relatively low levels of activity against the cellular DNA polymerase cm, with Kg values of 175 and 3.8,uM, respectively. (S)-Penciclovir-triphosphate did inhibit DNA synthesis by HSV-2 DNA polymerase with a defined template-primer, although it was not an obligate chain terminator like acydovir-triphosphate. These results provide a biochemical rationale for the highly selective and effectiv
L Stahle - One of the best experts on this subject based on the ideXlab platform.
-
distribution to the skin of Penciclovir after oral famciclovir administration in healthy volunteers comparison of the suction blister technique and cutaneous microdialysis
Acta Dermato-venereologica, 1999Co-Authors: N Borg, E Gotharson, Eva Benfeldt, L Groth, L StahleAbstract:Penciclovir is a drug active against herpes simplex viruses located in the epidermis basal layer. The aim of this study was to compare the suction blister technique and microdialysis as methods to measure the Penciclovir concentration in the skin after a single dose (250 mg) of its prodrug, famciclovir. Suction blister fluid, microdialysates and plasma were sampled from 11 healthy volunteers for 5 h after famciclovir administration. Both the suction blister technique and microdialysis showed that Penciclovir reaches the skin in concentrations sufficient to inhibit herpes virus replication. The maximum concentration in both suction blister fluid and in microdialysate was observed later than in plasma. The microdialysis concentration was decreased by cooling of the skin surface and by adrenaline-mediated vasoconstriction. The microdialysis recovery of Penciclovir was studied with respect to the flow-rate of perfusion medium through the microdialysis probe. Microdialysis and the suction blister technique can be used to study the time-concentration profile of Penciclovir in the skin and microdialysis allows a continuous sampling of the drug for a prolonged time after administration.
-
distribution to the skin of Penciclovir after oral famciclovir administration in healthy volunteers comparison of the suction blister technique and cutaneous microdialysis
Acta Dermato-venereologica, 1999Co-Authors: N Borg, E Gotharson, Eva Benfeldt, L Groth, L StahleAbstract:Penciclovir is a drug active against herpes simplex viruses located in the epidermis basal layer. The aim of this study was to compare the suction blister technique and microdialysis as methods to measure the Penciclovir concentration in the skin after a single dose (250 mg) of its prodrug, famciclovir. Suction blister fluid, microdialysates and plasma were sampled from 11 healthy volunteers for 5 h after famciclovir administration. Both the suction blister technique and microdialysis showed that Penciclovir reaches the skin in concentrations sufficient to inhibit herpes virus replication. The maximum concentration in both suction blister fluid and in microdialysate was observed later than in plasma. The microdialysis concentration was decreased by cooling of the skin surface and by adrenalinemediated vasoconstriction. The microdialysis recovery of Penciclovir was studied with respect to the flow-rate of perfusion medium through the microdialysis probe. Microdialysis and the suction blister technique can be used to study the timeconcentration profile of Penciclovir in the skin and microdialysis allows a continuous sampling of the drug for a prolonged time after administration. Key words: famciclovir; vasoconstriction; dermal drug concentration; temperature; microdialysis.