Research Article Pilot Study to Evaluate the Safety and Therapeutic Efficacy of Topical Oxifulvic Acid in Atopic Volunteers J.R. Snyman, 1,n J. Dekker, 2 S.C.K. Malfeld, 3 and C.E.J. van Rensburg 1 1 Department of Pharmacology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa 2 Enerkom (Pty) Ltd, Pretoria, South Africa 3 Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa Strategy, Management and Health Policy Venture Capital Enabling Technology Preclinical Research Preclinical Development Toxicology, Formulation Drug Delivery, Pharmacokinetics Clinical Development Phases I-III Regulatory, Quality, Manufacturing Postmarketing Phase IV ABSTRACT The study objectives were to establish first the safety and second the therapeutic efficacy of topically applied oxifulvic acid compared to 1% hydrocortisone and placebo creams. Oxifulvic acid has established antiinflammatory properties in vitro. It also inhibits elicited ear inflammation in mice at concentrations of 4.5 and 9%. In this double-blind cross-over study, 23 healthy volunteers allergic to grass or house dust mite allergen were recruited and included after signing informed consent. During the initial run-in period all volunteers were randomized to apply either 4.5 or 9% oxifulvic acid for 2 weeks on the volare aspect of one forearm (100 mm diameter) and rechallenged 21 days later to establish sensitization. Thereafter, volunteers were randomized to either placebo. 1% hydrocortisone, 4.5 or 9% oxifulvic acid creams. Creams were applied under occlusions 1 h prior to intradermal allergen challenge and every 8 h thereafter for 3 days (21-day intervals). The surface areas of the immediate and late phase skin reactions were calculated. Liver and kidney function tests as well as full blood counts were done at screening and thereafter weekly for the first 2 weeks and then at each follow-up visit. Topically applied oxifulvic acid had no significant effect on any of the safety parameters and also did not induce sensitization when applied on the skin. Oxifulvic acid (4.5%) caused inhibition of the elicited inflammatory reaction at 15 min and differed significantly from the 9% cream at 24 h. These changes were similar to that caused by hydrocortisone. No other significant changes were detected. Drug Dev. Res. 57:40–43, 2002.  c 2002 Wiley-Liss, Inc. Key words: oxifulvic acid; atopy; safety INTRODUCTION Fulvic acid is one of the components of the so- called humic substances which are naturally formed during thc decay of plant and animal residues [MaCarthe et al., 1985]. Humic substances can be divided into humic acid, fulvic acid, and humin, based on their solubility in water. Humic acids are known to have some therapeutic benefit and have been used for the treatment of various diseases such as inflammation, hypercholesterolemia, and Von Willebrand’s disease [Salz, 1974; Solovyeva and Lotosh, 1984; Lopez- Fernandez et al., 1992]. The evidence for therapeutic use of fulvic acids is, however, sparse. In vitro experiments [Wang et al., 1996] found that fulvic acid from peat possesses free radical scavenging properties. DDR Contract grant sponsors: Enerkom (Pty) Ltd.; Technology and Human Resources for Industry Programmes (THRIP) of the National Research Foundation; Department of Trade and Industry. n Correspondence to: J.R. Snyman, Dept. of Pharmacology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa. Published online in Wiley InterScience (www.interscience. wiley.com) DOI: 10.1002/ddr.10116 DRUG DEVELOPMENT RESEARCH 57:40–43 (2002)  c 2002 Wiley-Liss, Inc.