Renova Retin-A
Simultaneous determination of tretinoin and clindamycin phosphate and their degradation products in topical formulations by reverse phase HPLC.

Ye YR, Bektic E, Buchta R, Houlden R, Hunt B.

Connetics Australia Pty. Ltd, 8 Macro Crt, Rowville, VIC 3178, Australia. Rye connetics.com.au

A new HPLC method based on reverse phase separation and photodiode-array detection has been developed for the simultaneous determination of tretinoin and clindamycin phosphate, and their degradation products in topical formulations. The method has been shown to be stability indicating, accurate, and precise for two different formulation vehicles. Separation was achieved on a reverse phase C18 column (Lichrospher, RP18, 5 microm, 25 cm x 4.6 mm ID, Phenomenex, USA) using a simple gradient with aqueous-acetonitrile and aqueous-methanol mobile phases. The method recovery averaged 100.3% for tretinoin and 99.6% for clindamycin phosphate at a concentration range between 80% and 120% of the label claim. The method can be applied to assess the stability of tretinoin and clindamycin phosphate in pharmaceutical formulations containing tretinoin and clindamycin phosphate individually or in combination as active drugs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15335061&dopt=Abstract tretinoin Retin-A Renova



Renova Retin-A
Steady-state mRNA levels of interleukin-1, integrins, cJun, and cFos in hairless mouse skin during short-term chronic UV exposure and the effect of topical tretinoin.

Kligman LH, Yang S, Schwartz E.

Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.

We have proposed that UV activation of cytokine and integrin signaling pathways may initiate the photoaging process and that one of the effects of tretinoin treatment may be to alter the cytokine and integrin patterns. In previous results, steady-state mRNA levels of interleukin-1alpha, tumor necrosis factor alpha, transforming growth factor beta, collagenase, stromelysin, collagen, and integrins (alpha1 and alpha2) were increased in the skin of hairless mice that were either UV treated or concurrently treated with UV followed by topical tretinoin for 5 weeks. The aim of this study was to focus on the expression of alpha1, alpha2 and alpha5 integrins, IL-1alpha, IL-1beta, cJun, and cFos at an earlier time point (3 weeks). Animals were UV irradiated thrice weekly for 3 weeks and were treated topically with either 0.05% tretinoin or the vehicle immediately after each exposure. Total RNA was prepared and used in RT-PCR with radiolabeled dCTP and specific primers. UV slightly increased steady-state mRNA levels for alpha1, alpha2 and alpha5 integrins whereas UV + tretinoin increased their expression (3-, 2- and 7-fold respectively). Steady-state mRNA levels for IL-1alpha, IL-1beta and cJun were increased with UV (3-, 12- and 6-fold respectively) and with UV + tretinoin (6-, 7- and 9-fold respectively). In contrast, cFos expression was unchanged. In situ staining for IL-1alpha mRNA was slightly more abundant in mice treated for 3 weeks with UV and UV + tretinoin than in controls whereas 5 weeks of UV + tretinoin treatment gave strongly positive staining. Results are consistent with cytokines and integrins mediating the effects of UV on the skin, with modulation of these effects by tretinoin.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10540944&dopt=Abstract tretinoin Retin-A Renova



Renova Retin-A
Treatment of extra-abdominal desmoid tumors with interferon-alpha with or without tretinoin.

Leithner A, Schnack B, Katterschafka T, Wiltschke C, Amann G, Windhager R, Kotz R, Zielinski CC.

Department of Orthopedic Surgery, University Hospital, Vienna, Austria.

BACKGROUND AND OBJECTIVES: Surgery is the main treatment for extra-abdominal desmoid tumors, but the results of further management remain uncertain. Therefore, a retrospective analysis was undertaken to evaluate the toxicity and efficacy of treatment with interferon-alpha (IFN-alpha) +/- tretinoin in this setting. METHODS: Thirteen patients with extra-abdominal desmoid tumors and a median age of 32 years (range, 15-73) received IFN-alpha. Seven of these patients received a combination of IFN-alpha and tretinoin in order to test further enhancement. RESULTS: After a mean observation period of 27 +/- 15 months (mean +/- standard deviation) under treatment with IFN-alpha +/- tretinoin, local control was seen in 11 of 13 patients (85%). Seven patients had no evidence of disease at a mean disease-free interval of 22 +/- 18 months; in two patients progressive disease occurred after only 7 and 9 months, respectively, of observation. In another four patients, progression of the desmoid tumor was stabilized. CONCLUSIONS: The data of this retrospective, nonrandomized study on therapy with IFN-alpha +/- tretinoin suggest that such treatment may be effective in prolonging the disease-free interval of patients after intralesional or marginal surgery. Because of the encouraging response rate, this regimen appears to be another nonsurgical treatment alternative. Copyright 2000 Wiley-Liss, Inc.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10649274&dopt=Abstract tretinoin Retin-A Renova



Renova Retin-A
Evidence for a probable causal relationship between tretinoin, acitretin, and etretinate and intracranial hypertension.

Fraunfelder FW, Fraunfelder FT.

Casey Eye Institute, Oregon Health & Science University, 3375 SW Terwilliger Boulevard, Portland, OR 97201, USA. eyedrug ohsu.edu

With the recognition that vitamin A and isotretinoin may cause intracranial hypertension, the authors reviewed 331 case reports of ocular side effects associated with the three other marketed retinoids: tretinoin, acitretin, and etretinate. The reports were drawn from the National Registry of Drug-Induced Ocular Side Effects, the World Health Organization (WHO), the Food and Drug Administration, and medical journals between 1979 and 2003. There were 21 cases of intracranial hypertension associated with these three retinoids, leading to an inference that they are probably causally related to intracranial hypertension by WHO criteria. The lack of positive rechallenge data precludes the inference of a definite causal relationship to intracranial hypertension by WHO criteria. The inference of an independent causal role of these retinoids is further cautioned by the fact that six patients were concurrently using tetracycline or minocycline. Even so, the data suggest that all retinoids may, in rare instances, cause intracranial hypertension.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15348987&dopt=Abstract tretinoin Retin-A Renova