Does Iatrogenic Scleroderma due to Injection-Site Reaction to Enfuvirtide Impair Absorption of the Drug?

• Published in: Clinical drug investigation 2008-01, Vol.28 (5), p.305-311
• Main Authors: Maggi, Paolo, Filotico, Raffaele, Bonora, Stefano, Volpe, Anna, Bellacosa, Chiara, Cinori, Eliana, de Requena, Daniel Gonzalez, D’Avolio, Antonio, Di Perri, Giovanni
• Format: Article
• Language: English
• Subjects: Adult; Anti-HIV Agents - adverse effects; Anti-HIV Agents - pharmacokinetics; Area Under Curve; Female; HIV Envelope Protein gp41 - adverse effects; HIV Envelope Protein gp41 - pharmacokinetics; Humans; Iatrogenic Disease; Injections, Intravenous - adverse effects; Internal Medicine; Male; Medicine; Medicine & Public Health; Middle Aged; Original Research Article; Peptide Fragments - adverse effects; Peptide Fragments - pharmacokinetics; Pharmacology/Toxicology; Pharmacotherapy; Scleroderma, Localized - chemically induced; Scleroderma, Localized - metabolism; Skin - pathology; Urticaria - pathology; Vasculitis - pathology
• ISSN: 1173-2563; 1179-1918
• DOI: 10.2165/00044011-200828050-00004

Background: Chronic iatrogenic scleroderma is a possible obstacle to the absorption of subcutaneously administered drugs. This study correlated the clinical and histopathological pattern of injection-site reactions (ISRs) to the pharmacokinetics of enfuvirtide in patients with HIV . Methods: Fourteen patients treated with an enfuvirtide-based antiretroviral regimen for a median of 45 weeks were enrolled and their ISRs were evaluated. Twelve patients with evidence of ISRs underwent cutaneous biopsies using a 4-mm punch. The maximum plasma enfuvirtide concentration (Cmax) and the area under the enfuvirtide concentration-time curve (AUC) were assessed using blood sampling. Results: Four different macroscopic patterns of ISR were identified: A — no evidence of cutaneous lesions; B — transient infiltrative lesions that auto-resolved within 24 hours; C — transient nodular lesions that auto-resolved within 7–15 days; and D–stable lesions after more than 30 days. Histological examination showed three morphological patterns: (1) acute urticaria/vasculitis-like pattern, (2) subacute pattern and (3) chronic scleroderma-like pattern. No differences among patients with the various patterns of ISRs were observed, except for a higher C max and AUC in patients with pattern 1. Conclusions: These results confirm that although iatrogenic scleroderma is not related to impaired enfuvirtide absorption, higher C max and AUC values are observed in patients with urticaria/vasculitis-like patterns.