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(A). LC-MS Spectra of Metabolites Formed Following Incubation of 14 C-loratadine with CYP3A4 and CYP2C19 SUPERSOMES. (B). LC-MS/MS Spectra of Hydroxylated Loratadine Metabolites (M53, M54a and Loratadine).
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The present study demonstrated that in addition to CYP3A4 and CYP2D6, the metabolism of loratadine is also catalyzed by CYP1A1, CYP2C19, and to a lesser extent by CYP1A2, CYP2B6, CYP2C8, CYP2C9 and CYP3A5. The biotransformation of loratadine was associated with the formation of desloratadine (DL) and further hydroxylation of both DL and the parent...
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... incubation with different CYP450 Supersomes were characterized using LC-MS and LC-MS/MS experiments. The prominent metabolites detected were desloratadine (DL, M49), 5-OH DL (M33), 6-OH DL (M31), and several hydroxylated loratadine metabolites (M53, M54, M54a, and M54b). LC-MS spectra of loratadine and several of these metabolites are shown in Fig. (4A). The most predominant peak in each mass spectrum corresponds to the protonated molecule of each compound. Therefore, the mass-to-charge ratio (m/z) of these protonated molecules provides the molecular weight (MW) of each compound. For example, the m/z value measured for DL is 311 Th, which translates the MW to be 310 Da. This value is ...
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... 311 Th, which translates the MW to be 310 Da. This value is 72 Da lower than that for loratadine (382 Da). Therefore, DL is most likely formed by descarboethoxylation of loratadine. Further, the presence of a Cl atom in loratadine facilitated the detection of all metabolites due to the unique 35 Cl/ 37 Cl natural isotope abundances. As shown in Fig. (4A), the protonated molecule in all mass spectra depicts a 3:1 ratio for ion intensities and serving as a marker for loratadine-derived molecules. Additional structural details were obtained using LC-MS/MS spectroscopy and comparing LC-MS and LC-MS/MS spectra and retention times of metabolites with those of reference standards, when ...
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... LC-MS/MS spectra of loratadine and two hydroxylated metabolites are shown in Fig. (4B). Protonated molecules of loratadine (m/z = 383 Th) fragmented to produce ions at m/z 337, 294, and 259 Th. The proposed structures of these fragment ions are shown in Fig. (5). The consecutive loss of C 2 H 5 OH and NH=CO are indicative of an intact carboethoxy moiety in loratadine and can be used to demonstrate whether a metabolite ...
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... and 259 Th. The proposed structures of these fragment ions are shown in Fig. (5). The consecutive loss of C 2 H 5 OH and NH=CO are indicative of an intact carboethoxy moiety in loratadine and can be used to demonstrate whether a metabolite has undergone modifications in this region or in the remaining portion of the molecule. The LC-MS spectra (Fig. 4A) of hydroxylated metabolites of loratadine (M53, M54, M54a, M54b) demonstrated extensive dehydration in the ion source that resulted in the formation of an ion at 381 Th. This observation indicates that hydroxylation in these metabolites are aliphatic in nature. The ion at m/z 381 was further fragmented in MS/MS experiments to generate ...
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... dehydration in the ion source that resulted in the formation of an ion at 381 Th. This observation indicates that hydroxylation in these metabolites are aliphatic in nature. The ion at m/z 381 was further fragmented in MS/MS experiments to generate structural information on these metabolites. The MS/MS spectra of M53 and M54a are shown in Fig. (4B). ...
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... MS/MS spectra (not shown) of M54 and M54b are similar to that of M53 and M54a, respectively. The proposed structures of fragment ions are shown in Fig. (5). Both mass spectra indicate that the hydroxylation did not occur in the carboethoxy moiety. The presence of the fragment ion at 228 Th in the fragmentation spectrum of M54a (Fig. 4B, bottom panel) indicates that in M54a the hydroxylation was not in the tricyclic ring system and therefore must be in the piperidine ring of loratadine. In contrast, the absence of ions at 228 and 280 Th indicates that hydroxylation in M53 is most likely on the bridgehead of the tricyclic ring moiety. Similarly the hydroxylation in M54 and 54b is ...
Citations
... lOR is a tricyclic antihistamine, which acts as a selective inverse agonist of peripheral histamine h-1 receptors (Devillier et al., 2008). after being absorbed from the gastrointestinal tract, it is metabolized in the liver by several isoenzymes of the cytochrome P450 system (Ghosal et al., 2009). lOR inhibits the inflammatory response through the NFk B pathway by binding with the syk and src proteins (hunto et al., 2020). ...
This study employed computational modelling (in silico) methods, combined with ecotoxicological experiments (in vivo) to predict the persistence/biodegradability, bioaccumulation, mobility, and ecological risks of an antihistamine drug (Loratadine: LOR) in the aquatic compartment. To achieve these goals, four endpoints of the LOR were obtained from different open-source computational tools, namely: (i) “STP total removal"; (ii) Predicted ready biodegradability; (iii) Octanol-water partition coefficient (KOW); and (iv) Soil organic adsorption coefficient (KOC). Moreover, acute and chronic, ecotoxicological assays using non-target freshwater organisms of different trophic levels (namely, algae Pseudokirchneriella subcapitata; microcrustaceans Daphnia similis and Ceriodaphnia dubia; and fish Danio rerio), were used to predict the ecological risks of LOR. The main results showed that LOR: (i) is considered persistent (after a weight-of-evidence assessment) and highly resistant to biodegradation; (ii) is hydrophobic (LOG KOW = 5.20), immobile (LOG KOC = 5.63), and thus, it can potentially bioaccumulate and/or can cause numerous deleterious effects in aquatic species; and (iii) after ecotoxicological evaluation is considered "toxic" and/or “highly toxic” to the three trophic levels tested. Moreover, both the ecotoxicological assays and risk assessment (RQ), showed that LOR is more harmful for the crustaceans (RQcrustaceans = moderate to high risks) than for algae and fish. Ultimately, this study reinforces the ecological concern due to the indiscriminate disposal of this antihistamine drug in worldwide aquatic ecosystems.
... 1) It is often used to treat allergic diseases in Chinese children, such as seasonal allergies and rashes (Clissold et al., 1989). 2) Loratadine is known to be a substrate for CYP2D6 based on previous in vitro studies (Yumibe et al., 1996;Ghosal et al., 2009;Sheludko et al., 2018). CYP2D6 is the enzyme that plays an important role in the pharmacokinetic variability of loratadine in Chinese population. ...
... Loratadine was selected in our present study, not only because of its routine use and determinant role of CYP2D6 on its metabolism, but also the ethical reason. Although CYP3A4, CYP2D6, and CYP2C19 are involved in the metabolism of loratadine (Yumibe et al., 1996;Ghosal et al., 2009), the efficiency of loratadine conversion by CYP2D6 was 4.5∼5-fold higher than that of CYP3A4 (Yumibe et al., 1996;Ghosal et al., 2009;Sheludko et al., 2018) and CYP2D6*10 allele accouts for approximately 50% in Asian subjects (Johansson et al., 1994). For CYP3A4, many variant alleles such as CYP3A4*1B, *2, and *3 are absent in Chinese subjects (Walker et al., 1998;Sata et al., 2000;van Schaik et al., 2001). ...
... Loratadine was selected in our present study, not only because of its routine use and determinant role of CYP2D6 on its metabolism, but also the ethical reason. Although CYP3A4, CYP2D6, and CYP2C19 are involved in the metabolism of loratadine (Yumibe et al., 1996;Ghosal et al., 2009), the efficiency of loratadine conversion by CYP2D6 was 4.5∼5-fold higher than that of CYP3A4 (Yumibe et al., 1996;Ghosal et al., 2009;Sheludko et al., 2018) and CYP2D6*10 allele accouts for approximately 50% in Asian subjects (Johansson et al., 1994). For CYP3A4, many variant alleles such as CYP3A4*1B, *2, and *3 are absent in Chinese subjects (Walker et al., 1998;Sata et al., 2000;van Schaik et al., 2001). ...
Objective: The elucidation of CYP2D6 developmental pharmacogenetics in children has improved, however, these findings have been largely limited to studies of Caucasian children. Given the clear differences in CYP2D6 pharmacogenetic profiles in people of different ancestries, there remains an unmet need to better understand the developmental pharmacogenetics in populations of different ancestries. We sought to use loratadine as a substrate drug to evaluate the effects of ontogeny and pharmacogenetics on the developmental pattern of CYP2D6 in Chinese pediatric patients.
Methods: Chinese children receiving loratadine treatment were enrolled in the present study. The metabolite-to-parent ratio (M/P ratio), defined as the molar ratio of desloratadine to loratadine of trough concentrations samples at steady-state condition, was used as a surrogate of CYP2D6 activity. Loratadine and desloratadine were determined by LC/MS/MS method. Variants of CYP2D6 were genotyped by polymerase chain reaction for CYP2D6 *4, *10, *41 and long polymerase chain reaction for CYP2D6 *5.
Results: A total of 40 patients were available for final analysis. The mean age was 4.50 (range 0.50–9.00) years and the mean weight was 19.64 (range 7.00–42.00) kg. The M/P ratio was significantly lower in intermediate metabolizers (IMs) compared to normal metabolizers (NMs) (10.18 ± 7.97 vs. 18.80 ± 15.83, p = 0.03). Weight was also found to be significantly associated with M/P ratio (p = 0.03).
Conclusion: The developmental pharmacogenetics of CYP2D6 in Chinese children was evaluated using loratadine as a substrate drug. This study emphasizes the importance of evaluating the developmental pharmacogenetics in populations of different ancestries.
... According to the literature, these compounds are partly metabolized by the polymorphic CYP2D6 enzyme. Because these are old drugs, no patient data but only in vitro studies are available121314 [15] [17]. It seems rational to assume that PMs will have higher drug exposure at normal doses than EMs. ...
Drug safety and efficacy are highly variable among patients. Most patients will experience the desired drug effect, but some may suffer from adverse drug reactions or gain no benefit. Pharmacogenetic testing serves as a pre-treatment diagnostic option in situations where failure or adverse events should be avoided at all costs. One such situation is human space flight. On the international space station (ISS), a list of drugs is available to cover typical emergency settings, as well as the long-term treatment of common conditions for the use in self-medicating common ailments developing over a definite period. Here, we scrutinized the list of the 78 drugs permanently available at the ISS (year 2014) to determine the extent to which their metabolism may be affected by genetic polymorphisms, potentially requiring genotype-specific dosing or choice of an alternative drug. The purpose of this analysis was to estimate the potential benefit of pharmacogenetic diagnostics in astronauts to prevent therapy failure or side effects.
... In 2001, desloratadine was approved as a drug in its own right; however, at the time of its approval, the enzymology surrounding amounts in urine and feces (Ramanathan et al., 2007). Conventional in vitro systems such as recombinant P450 enzymes, human liver microsomes (HLM) and human liver S9 fractions do not convert desloratadine to 3-hydroxydesloratadine; hence, its enzymology and the basis for certain individuals being identified as poor metabolizers of desloratadine have remained a mystery for many years (Prenner et al., 2006; Ghosal et al., 2009). Previously, we demonstrated that cryopreserved human hepatocytes (CHH) can form 3-hydroxydesloratadine, as can HLM provided they are supplemented with both NADPH and UDP-glucuronic acid (UDP-GlcUA) (Kazmi et al., 2015). ...
... Henz, 2001). The major human circulating metabolite of desloratadine is 3-hydroxydesloratadine, a metabolite whose enzymology remained a mystery for over 20 years due, in large part, to the inability of conventional in vitro test systems, such as subcellular fractions, to form 3-hydroxydesloratadine (Ghosal et al., 2009). As described previously, we demonstrated that CHH are capable of forming 3-hydroxydesloratadine, with a K m of 1.6 μ Furthermore, recombinant CYP2C8 was also incapable of converting desloratadine to 3-hydroxydesloratadine despite catalyzing high rates of metabolism of substrates like paclitaxel and amodiaquine. ...
Desloratadine (Clarinex), the major active metabolite of loratadine (Claritin), is a non-sedating antihistamine used for the treatment of seasonal allergies and hives. Previously we reported that the formation of 3-hydroxydesloratadine, the major human metabolite of desloratadine, involves three sequential reactions, namely N-glucuronidation by UGT2B10 followed by 3-hydroxylation by CYP2C8 followed by de-conjugation (rapid, non-enzymatic hydrolysis of the N-glucuronide). In this study we assessed the perpetrator potential of desloratadine based on in vitro studies of its inhibitory effects on cytochrome P450 and UDP-glucuronosyltransferase (UGT) enzymes in human liver microsomes (HLM). Desloratadine (10 μM) caused no inhibition (<15%) of CYP1A2, CYP2C8, CYP2C9, or CYP2C19 and weak inhibition (32-48%) of CYP2B6, CYP2D6 and CYP3A4/5. In cryopreserved human hepatocytes (CHH), which can form the CYP2C8 substrate desloratadine N-glucuronide, desloratadine did not inhibit the CYP2C8-dependent metabolism of paclitaxel or amodiaquine. Assessment of UGT inhibition identified desloratadine as a potent and relatively selective competitive inhibitor of UGT2B10 (Ki value of 1.3 μM). Chemical inhibition of UGT enzymes in HLM demonstrated that nicotine (UGT2B10 inhibitor) but not hecogenin (UGT1A4 inhibitor) completely inhibited the conversion of desloratadine (1 μM) to 3-hydroxydesloratadine in HLM fortified with both NADPH and UDP-glucuronic acid. 3-Hydroxydesloratadine formation correlated well with levomedetomidine glucuronidation (UGT2B10 marker activity) with a panel of individual CHH (r(2) = 0.72). Overall, the results of this study confirm the role of UGT2B10 in 3-hydroxydesloratadine formation and identify desloratadine as a selective in vitro inhibitor of UGT2B10.
The American Society for Pharmacology and Experimental Therapeutics.
... 2001/21165lbl.pdf). Ghosal et al. (2009) examined the metabolism of loratadine and further characterized the in vitro enzymology of the metabolites using pooled human liver microsomes (HLMs) and recombinant cytochrome P450 (P450) enzymes, demonstrating that desloratadine, 5-hydroxydesloratadine, and 6-hydroxydesloratadine formation could be mediated by CYP3A4, CYP2D6, and CYP2C19. However, they were unable to detect 3-hydroxydesloratadine in either in vitro test system and therefore were unable to identify which enzyme or enzymes were involved in its formation. ...
... The results for 3-hydroxydesloratadine formation with 1 mM desloratadine are shown in Fig. 1 (10 mM desloratadine data were similar and not shown). 3-Hydroxydesloratadine formation was not observed in any HLM or HS9 sample, consistent with previous reports (Ghosal et al., 2009). However, 3-hydroxydesloratadine was detected in CHHs as early as 30 minutes, with linear metabolite formation up to 4 hours. ...
... The data are summarized in Table 1. No 3-hydroxydesloratadine was detected in any recombinant P450 or FMO enzyme sample tested, consistent with previously reported findings (Ghosal et al., 2009). Both 5-hydroxydesloratadine and 6-hydroxydesloratadine were readily formed by CYP1A1, CYP2D6, and CYP3A4, with trace metabolite formation observed for several other P450 enzymes (Table 1). ...
Desloratadine (Clarinex(®)), the major active metabolite of loratadine (Claritin(®)), is a non-sedating long-lasting antihistamine widely used for the treatment of allergic rhinitis and chronic idiopathic urticaria. For over 20 years, it has remained a mystery as to which enzymes are responsible for the formation of 3-hydroxydesloratadine, the major active human metabolite, largely due to the inability of any in vitro system tested thus far to generate this metabolite. In this study, we demonstrated that cryopreserved human hepatocytes (CHH) form 3-hydroxydesloratadine and its corresponding O-glucuronide. CHHs catalyzed the formation of 3-hydroxydesloratadine with a Km of 1.6 μM and Vmax of 1.3 pmol/min/million cells. Chemical inhibition of cytochrome P450 (CYP) enzymes in CHH demonstrated that gemfibrozil glucuronide (CYP2C8 inhibitor) and 1-aminobenzotriazole (general P450 inhibitor) inhibited 3-hydroxydesloratadine formation by 91% and 98%, respectively. Other inhibitors of CYP2C8 (gemfibrozil, montelukast, clopidogrel glucuronide, repaglinide and cerivastatin) also caused extensive inhibition of 3-hydroxydesloratadine formation (73-100%). Assessment of desloratadine, amodiaquine and paclitaxel metabolism by a panel of individual CHHs demonstrated that CYP2C8 marker activity robustly correlated with 3-hydroxydesloratadine formation (r(2) of 0.70-0.90). Detailed mechanistic studies with sonicated or saponin-treated CHHs, human liver microsomes and S9 fractions showed that both NADPH and UDP-glucuronic acid are both required for 3-hydroxydesloratadine formation, and studies with recombinant UGT and CYP enzymes implicated the specific involvement of UGT2B10 in addition to CYP2C8. Overall, our results demonstrate for the first time that desloratadine glucuronidation by UGT2B10, followed by CYP2C8 oxidation and a de-conjugation event are responsible for the formation of 3-hydroxydesloratadine.
The American Society for Pharmacology and Experimental Therapeutics.
... 7for structures), together accounting for approximately 18% of the dose in excreta. This pathway has also been demonstrated with other carbamate esters (Yumibe et al., 1996;Schmidt et al., 2006;Ghosal et al., 2009). Oxidation of the cyclopentene ring formed the major circulating metabolite S12 (LSN3049319, presented in plasma only) as well as the major fecal metabolite S10. ...
The disposition and metabolism of LY2452473 (a selective androgen receptor modulator, SARM) in humans were characterized after a single 15 mg (100 μCi) oral dose of [(14)C]LY2452473 to six healthy male subjects. LY2452473 was absorbed rapidly (plasma T(max) 2~3h for both LY2452473 and total radioactivity) and cleared slowly (plasma terminal t(1/2) of 27 h for LY2452473 and 51 h for the total radioactivity). LY2452473, metabolites S5 (acetylamine) and S12 (hydroxylation on the cyclopentene) were major circulating entities in plasma, accounting for approximately 42%, 21% and 35% of the total radioactivity exposure, respectively, as calculated from relative AUC(0-48) derived from the plasma radiochromatograms. The radioactive dose was almost completely recovered after 312 hours with 47.9% of the dose eliminated in urine and 46.6% in feces. Minimal LY2452473 was detected in excreta, indicating that metabolic clearance was the main route of elimination. Multiple metabolic pathways were observed with no single metabolic pathway accounting for more than 30% of the dose in excreta. Metabolite S10 (a diol across the cyclopenta-indole linkage) was the largest excretory metabolite (approximately 14% of the dose). S10 displayed interesting chemical and chromatographic properties, undergoing conversion to the corresponding epoxide under acidic conditions and converted back to the diol under neutral conditions. Multiple cytochromes P450 were involved in the formation of S4 (primary amine precursor of S5) and S12. CYP2C19 and CYP2D6 were the most active enzymes for the formation of S4 while CYP3A4 was the most active enzyme for the formation of S12 and depletion of LY2452473.
... There were no statistically significant differences in the mean plasma concentrations in any of the main pharmacokinetic parameters of rupatadine, DL, and 3-hydroxydesloratadine when administered in combination with azithromycin or alone [5] [6]. As of now, there have been several methods reported for quantification of DL in rat plasma with LC-MS [7], human plasma with LC-MS [8] [9] [10] [11] [12], LC-MS with nanospray ionization [13], human plasma with HPLC [14] [15] [16], dog plasma with HPLC [17], pharmaceutical formulation with HPLC [18] [19], and pharmaceutical formulation with electrophorsis [20]. Wen et al. [8] reported having developed a method using LLE with a concentration range of 0.1–20 ng/mL. ...
A simple, sensitive, and specific liquid chromatography tandem mass spectrometry (LC-MS/ MS) method was developed for the quantification of desloratadine (DL) in human plasma using desloratadine-d5 (DLD5) as an internal standard (IS). Chromatographic separation was performed using an Xbridge C18 column (50 mm  4.6 mm, 5 mm) with an isocratic mobile phase composed of 10 mM ammonium formate: methanol (20:80, v/v), at a flow rate of 0.7 mL/min. DL and DLD5 were detected with proton adducts at m/z 311.2-259.2 and 316.2-264.3 in multiple reaction monitoring (MRM) positive modes, respectively. Liquid–liquid extraction (LLE) method was used to extract the drug and the IS. The method was validated over a linear concentration range of 5.0–5000.0 pg/mL with a correlation coefficient of (r 2)Z0.9994. This method demonstrated intra-and inter-day precision within 0.7–2.0% and 0.7–2.7%, and an accuracy within 101.4–102.4%, and 99.5–104.8%. DL was found to be stable throughout the freeze–thaw cycles, bench-top, and postoperative stability studies. This method was successfully applied in the analysis of plasma samples following oral administration of DL (5 mg) in 35 healthy Indian male human volunteers under fasting conditions. & 2012 Xi'an Jiaotong University. Production and hosting by Elsevier B.V. All rights reserved.
... In cases of chronic idiopathic urticaria once-daily doses of 180 mg fexofenadine is recommended. Loratadine (9)(10)(11)(12) a class of medications called antihistamines and used to temporarily relieve the symptoms of hay fever (allergy to pollen, dust, or other substances in the air) and other allergies. These symptoms include sneezing, runny nose, and itchy eyes, nose, or throat. ...
High resolution RP-HPLC method has been developed for the simultaneous estimation of Psuedoephedrine, Fexofenadine and Loratadine in pharmaceutical products. Separation was achieved
by using C18, 150 x 4.6 mm, 5μm column at a temperature of 350C with a gradient mobile phase composed of sol-A: 0.01M pH 3.0 phosphate (KH2PO4) buffer, sol-B: Acetonitrile and gradient
program was 0-5min, sol-A: 80-60; 5-10min- sol-A: 60-20; 10-15min- sol-A: 20-20; 15-17min- sol-A: 20-80 and 17-20min- sol-A: 80-80. Flow rate was 0.60 ml per min and measured the
absorbance at 210nm. The retention time of Psuedoephedrine, Fexofenadine and Loratadine are 4.3min, 10.4min and 17.0min, respectively. The linearity of the proposed method was evaluated
from 5μg per mL to 100μg per mL and the correlation coefficient results were within the limit (not less than 0.999). The developed method has wide applicable for the quantification of
Psuedoephedrine, Fexofenadine and Loratadine in pharmaceutical dosage forms.
D Vitamini Kimyasal Yapısı ve Metabolizması Hülya Cenk D Vitamini Ve Genetik Aydın Rüstemoğlu D Vitamininin Normal Serum Düzeyleri, D Vitamin Düzeylerini Etkileyen Faktörler Ve D Vitamini Yetmezliği Sabiye Akbulut Serum D Vitamininin Ölçümü Andaç Uzdoğan, Çiğdem Yücel D Vitamini Biyoyararlanımı ve Doğal Beslenme Kaynakları Atilla Çifci, Halil İbrahim Yakut Sistemik D Vitamini Tedavi Ajanları, Biyoyararlanımı ve Tedavi Yönetimi Işıl Deniz Oğuz Topikal D Vitamini Tedavisi, Tedavi Yönetimi ve Kullanıldığı Hastalıklar Dursun Türkmen Deride D Vitamini Sentezi Mekanizmaları Abdullah Demirbaş, Ömer Faruk Elmas Güneşten Koruyucu Kullanımı ve D Vitamini Nursel Dilek, Yunus Saral D Vitamininin Deri Yapısı ve Fizyolojisine Etkisi Pelin Hızlı Deri Yaşlanması ve D Vitamini Ülker Gül Psoriasis ve D Vitamini Ülker Gül Psöriatik Artrit ve D Vitamini Mehmet Uçar Atopik Dermatit ve D Vitamini Ayşegül Ertuğrul, İlknur Bostancı Mast Hücresi ve Kutanöz Mastositozda D Vitamini Selçuk Doğan, Tülin Çataklı, İlknur Bostancı Ürtiker ve D Vitamini Kemal Özyurt Kaşıntı ve D Vitamini Kübra Yüce Atamulu Likenoid Dermatozlar ve D Vitamini Nihal Altunışık Vitiligo ve D Vitamini Ayşe Akbaş Melasma ve D Vitamini İbrahim Etem Arıca Rozase ve D Vitamini Nalan Saraç Akne ve D Vitamini Selma Korkmaz Hidradenitis Süpürativa ve D Vitamini Yılmaz Ulaş Seboreik Dermatit ve D Vitamini Dilek Başaran Otoimmün Büllöz Hastalıklar ve D Vitamini Sezgi Sarıkaya Solak Bağ Doku Hastalıkları ve D Vitamini Kevser Gök Behçet Hastalığı ve D Vitamini Şule Ketenci Ertaş, Ragıp Ertaş İdiyopatik Fotodermatozlar ve D Vitamini Bülent Nuri Kalaycı İktiyozis ve D Vitamini Tubanur Çetinarslan Epidermolizis Bülloza ve Vitamin D Eda Haşal Kseroderma Pigmentozum, Epidermodisplasia Verrusiformis ve D Vitamini Derya Yayla Nevüsler ve D Vitamini Serpil Şener, Suat Sezer Aktinik Keratoz ve Seboreik Keratozda D Vitamini Mahmut Sami Metin Deri Maliniteleri ve D Vitamini Sevda Önder Vaskülitler ve Vitamin D Havva Hilal Ayvaz Venöz Trombozis ve D Vitamini Cahit Yavuz Yara İyileşmesi ve D Vitamini Bülent Nuri Kalaycı Diyabetik Ayak Ülseri ve D Vitamini Gözde Ulutaş Demirbaş, Abdullah Demirbaş Granülomatöz Hastalıklar ve D Vitamini Selma Bakar Dertlioğlu Deri Enfeksiyonları ve Vitamin D Atıl Avcı Oral Mukoza Hastalıkları ve D Vitamini Ali İhsan Güleç Tırnak Sağlığı ve Hastalıklarında D Vitamini Hülya Cenk Alopesiler ve D Vitamini Munise Daye Hirsutizm ve D Vitamini Efşan Gürbüz Yontar Sistemik Kortikosteroid Kullanımında D Vitamini Desteği Selma Korkmaz Fototerapi ve D Vitamini Tuğba Özkök Akbulut Covıd-19 Ve Vitamin D Sibel Altunışık Toplu D Vitamini Tedavisinin Yan Etkileri ve D Vitamini Tedavisi Sürecinde Dikkat Edilecek Hususlar Dursun Türkmen, Nihal Altunışık D Vitamini Ve İlaç İlaç Etkileşimleri Şule Gökşin D Vitamini İntoksikasyonu Bedriye Müge SÖNMEZ
