Pidotimod: a review of its pharmacological features and clinical effectiveness in respiratory tract infections

References

• WHO. Acute respiratory infections: the forgotten pandemic. Bull World Health Organ. 1998;76:101–103.
   PubMed Web of Science ®Google Scholar
• WHO. 2018. Global Health Estimates (GHE): global deaths by cause, age and sex, 2000–2015; December, 2016. cited Aug 2018. Avaialble from: http://www.who.int/healthinfo/global_burden_disease/en/
   Google Scholar
• Fendrick AM, Monto AS, Nightengale B, et al. The economic burden of non-influenza-related viral respiratory tract infection in the United States. Arch Intern Med. 2003;163:487–494.
   PubMed Web of Science ®Google Scholar
• Chinese Paediatric Guidelines. Expert consensus on the diagnosis, treatment and management of recurrent upper respiratory tract infection in children. CJPP. 2017;32(10):721–725.
   Google Scholar
• de Benedictis FM, Bush A. Recurrent lower respiratory tract infections in children. BMJ. 2018 Jul 12;362:k2698. .
   PubMedGoogle Scholar
• Esposito S, Musio A. Immunostimulants and prevention of recurrent respiratory tract infections. J Biol Regul Homeost Agents. 2013;27:627–636.
   PubMed Web of Science ®Google Scholar
• Del-Rio-Navarro BE, Espinosa Rosales F, Flenady V, et al. Immunostimulants for preventing respiratory tract infection in children. Cochrane Database Syst Rev. 2006 Oct;18(4):CD004974.
   Google Scholar
• Coppi G, Falcone A, Manzardo S. Protective effects of pidotimod against experimental bacterial infections in mice. Arzneimittelforschung. 1994;44:1417–1421.
   PubMed Web of Science ®Google Scholar
• Dianzani C, Colangelo D, Tonso E, et al. In vivo antiviral effects of pidotimod. Arzneimittelforschung. 1994;44:1431–1433.
   PubMed Web of Science ®Google Scholar
• Migliorati G, Nicoletti I, Riccardi G. Immunomodulating activity of pidotimod. Arzneimittelforschung. 1994;44:1421–1424.
   PubMed Web of Science ®Google Scholar
• Taramelli D, Malabarba MG, Basilico N, et al. Effects of pidotimod on macrophage functions in methylprednisolone-treated mice. Arzneimittelforschung. 1994;44:1425–1430.
   PubMed Web of Science ®Google Scholar
• Giagulli C, Noerder M, Avolio M, et al. Pidotimod promotes functional maturation of dendritic cells and displays adjuvant properties at the nasal mucosa level. Int Immunopharmacol. 2009;9:1366–1373.
   PubMed Web of Science ®Google Scholar
• Carta S, Silvestri M, Rossi GA. Modulation of airway epithelial cell functions by Pidotimod: NF-kB cytoplasmatic expression and its nuclear translocation are associated with an increased TLR-2 expression. Ital J Pediatr. 2013;39:29.
   PubMed Web of Science ®Google Scholar
• Lawrence T. The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol. 2009;1:a001651.
   PubMed Web of Science ®Google Scholar
• Ferrario BE, Garuti S, Braido F, et al. Pidotimod: the state of art. Clin Mol Allergy. 2015;13:8.
   PubMedGoogle Scholar
• Riboldi P, Gerosa M, Meroni PL. Pidotimod: a reappraisal. Int J Immunopathol Pharmacol. 2009;22:255–262.
   PubMed Web of Science ®Google Scholar
• Zuccotti GV, Mameli C, Trabattoni D, et al. Immunomodulating activity of Pidotimod in children with Down syndrome. J Biol Regul Homeost Agents. 2013;27:253–258.
   PubMed Web of Science ®Google Scholar
• Mukherjee S, Karmakar S, Babu SP. TLR2 and TLR4 mediated host immune responses in major infectious diseases: a review. Braz J Infect Dis. 2016;20:193–204.
   PubMed Web of Science ®Google Scholar
• Calandra T, Roger T. Macrophage migration inhibitory factor: A regulator of innate immunity. Nat Rev Immunol. 2003;3:791–800.
   PubMed Web of Science ®Google Scholar
• Mailland F, Coppi G, Silingardi S. Pharmacokinetics and oral bioavailability of pidotimod in humans. Arzneimittelforschung. 1994;44:1465–1469.
   PubMed Web of Science ®Google Scholar
• D’Angelo L, De Ponti F, Crema F, et al. Effect of food on the bioavailability of pidotimod in healthy volunteers. Arzneimittelforschung. 1994;44:1473–1475.
   PubMed Web of Science ®Google Scholar
• Spotti D, Biffi M, Coppi G, et al. Pharmacokinetics of pidotimod in elderly volunteers and in renal failure patients. Arzneimittelforschung. 1994;44:1470–1472.
   PubMed Web of Science ®Google Scholar
• Coppi G, Amico-Roxas M, Bertè F, et al. Toxicological evaluation of pidotimod. Arzneimittelforschung. 1994;44(12A):1448–1453.
   PubMed Web of Science ®Google Scholar
• Adams K, Allen JA, Brooker PC, et al. Genotoxicity testing of Pidotimod in vivo and in vitro. Arzneim Forsch Drug Res. 1994;44:1454–1459.
   PubMed Web of Science ®Google Scholar
• Bisetti G, Ciappi G, Bariffi F, et al. Evaluation of the efficacy of Pidotimod on the exacerbations in patients affected with chronic bronchitis. Arzneim Forsch Drug Res. 1994;44:1499–1502.
   PubMed Web of Science ®Google Scholar
• Burgio GR, Marseglia GL, Severi F, et al. Immunoactivation by pidotimod in children with recurrent respiratory infections. Arzneimittelforschung. 1994;44(Suppl 12A):152–159.
   Web of Science ®Google Scholar
• Caramia G, Clemente E, Solli R, et al. Efficacy and safety of pidotimod in the treatment of recurrent respiratory infections in children. Arzneimittelforschung. 1994;44(Suppl12A):1480–1484.
   PubMedGoogle Scholar
• Careddu P. Role of immunoactivation with pidotimod in recurrent respiratory infections in childhood. Arzneimittelforschung. 1994;44(Suppl12A):1506–1511.
   PubMedGoogle Scholar
• Careddu P, Mei V, Venturoli V, et al. Pidotimod in the treatment of recurrent respiratory infections in paediatric patients. Arzneimittelforschung. 1994;44(Suppl12A):1485–1489.
   PubMedGoogle Scholar
• Motta G, De Campora E, De Vita C, et al. Immunoactivity of pidotimod against episodes of recurrent tonsillitis in childhood. Arzneimittelforschung. 1994;44(Suppl12A):1521–1524.
   PubMedGoogle Scholar
• Passali D, Calearo C, Conticello S. Pidotimod in the management of recurrent pharyngotonsillar infections in childhood. Arzneimittelforschung. 1994;44:1511–1516.
   PubMed Web of Science ®Google Scholar
• Ciaccia A. Pidotimod activity against chronic bronchitis exacerbations. Arzneim Forsch Drug Res. 1994;44:1516–1520.
   PubMed Web of Science ®Google Scholar
• La Mantia I, Grillo C, Mattina T, et al. Prophylaxis with the novel immunomodulator Pidotimod reduces the frequency and severity of upper respiratory tract infections in children with Down’s Syndrome. J Chemother. 1999;11:126–130.
   PubMed Web of Science ®Google Scholar
• Guo W, Liao Y, Chen W. Observation of the efficacy of pidotimod in combination with an antibiotic for treating acute sinusitis in children. China Practice Medicine. 2008;3(29):112–113
   Google Scholar
• Long M, Zhang J, Bai L-Y. Efficacy observation of pidotimod in the treatment of pediatric acute suppurative tonsillitis. China Pharm. 2011;22:1701–1702. [Translated from Chinese].
   Google Scholar
• Di Cicco M, Di Pasquale D, Rinaldi V. Analisi retrospettiva di una casistica pediatrica ORL sottoposta a trattamento con pidotimod. Argomenti Acta Otorhinolaryngol Italica. 2015;9:1–4. Italian.
   Google Scholar
• Buongiorno A, Pierossi N. Effectiveness of pidotimod in combination with bacterial lysates in the treatment of the pfapa (periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis) syndrome. Minerva Pediatr. 2015;67:219–226. Italian.
   PubMed Web of Science ®Google Scholar
• Yan Y. Changes of immune function in children with refractory mycoplasma pneumoniae pneumonia and effects of Pidotimod. J Clin Pediatr. 2008;26:570–572.
   Google Scholar
• Mao L, Guo Y. Effect of pidotimod combined with budesonide on MPP treatment and Th1/Th2 balance. J Radioimmunol. 2012;25:108–111.
   Google Scholar
• Esposito S, Garziano M, Rainone V, et al. Immunomodulatory activity of pidotimod administered with standard antibiotic therapy in children hospitalized for community-acquired pneumonia. J Transl Med. 2015;13:288.
   PubMed Web of Science ®Google Scholar
• Aivazis V, Hatzimichail A, Papachristou A, et al. Clinical evaluation and changes of the respiratory epithelium function after administration of Pidotimod in Greek children with recurrent respiratory tract infections. Minerva Pediatr. 2002;54:315–319.
   PubMedGoogle Scholar
• Chai M, Wu L, Yao D, et al. Efficacy observation of pidotimod in the treatment of 30 children patients with recurrent respiratory infection. Zhejiang Med J. 2006;12:1034–1037.
   Google Scholar
• Zhou Y, Dai Y-X. Comparison of effects of pidotimod and spleen aminopeptide on clinical symptoms and Th1/Th2 cytokine in children with RRI. Chin J Biochem Pharm. 2012;33:64–69.
   Google Scholar
• Liu C, Shen S. Immunologic function changes caused by repeated respiratory infection and pidotimod’s efficacies on them. Chin J Primary Med Pharm. 2012;19:2352–2354.
   Google Scholar
• Licari A, De Amici M, Nigrisoli S, et al. Pidotimod may prevent recurrent respiratory infections in children. Minerva Pediatr. 2014;66:363–367.
   PubMed Web of Science ®Google Scholar
• Namazova-Baranova LS, Alekseeva AA, Kharit SM, et al. Efficacy and safety of pidotimod in the prevention of recurrent respiratory infections in children: a multicentre study. Int J Immunopathol Pharmacol. 2014;27:413–419.
   PubMed Web of Science ®Google Scholar
• Mameli C, Pasinato A, Picca M, et al., AX-Working Group. Pidotimod for the prevention of acute respiratory infections in healthy children entering into daycare: A double blind randomized placebo-controlled study. Pharmacol Res. 2015;97:79–83.
   PubMed Web of Science ®Google Scholar
• Correa JBV, Espinosa Morales S, Bolaños Ancona JC, et al. Pidotimod in recurring respiratory infection in children with allergic rhinitis, asthma, or both conditions. Rev Alerg Mex. 2002;49:27–32. Spanish.
   PubMedGoogle Scholar
• Ma X, Sun X. The effect of Pidotimod on serum IL-4, IFN-gamma and IgE in asthmatic children. Chin J Biochem Pharm. 2011;32:400–403.
   Google Scholar
• Zhai F-X Liu LX. The effect of Pidotimod in the prevention and treatment of pediatric bronchial asthma. Chin J Biochem Pharm. 2011;32:151–155.
   Google Scholar
• Sun L-X, Yang X-S, Zhang D-J, et al. Influence of pidotimod on the IL-16, immunoglobulin and T cell subsets in asthmatic children. J Clin Pediatr. 2011;29:777–779. Chinese.
   Google Scholar
• Gaiduk IM, Trusova OV, Korostovtsev DS, et al. Application of pidotimod for the prevention of frequent acute respiratory infections in children with allergic respiratory diseases. Curr Pediatr. 2012;11:156–159.
   Google Scholar
• Liu J. Study on the influence of pidotimod on attack times, pulmonary function and immune function of children with asthma. Drugs Clin. 2013;10(12):1–9.
   Google Scholar
• Cogo R, Furcolo F, Monzani GP. Studio clinic sull’acido timodolico nel trattamento delle infezioni delle vie respiratorie. NAM. 1989;5:492–497.
   Google Scholar
• Guaramagna C, Perricone G. PGT/1A (acido timodolico)nel trattamento delle infezioni delle vie respiratorie del paziente anziano. Ital J Clin Res Ther. 1990;11:9–13.
   Google Scholar
• Pozzi E, Dolcetti A, Orlandi O, et al. Pidotimod in the treatment in patients affected by bacterial exacerbations of chronic bronchitis. Arzneim Forsch Drug Res. 1994;44:1495–1498.
   PubMed Web of Science ®Google Scholar
• Li X, Bai H. Treatment of 30 cases of senile pneumonia with Pidotimod. Clin Pharm. 2004;13:9.
   Google Scholar
• Cogo R. Valutazione sperimentale controllata dell’attività di Pidotimod in pazienti affetti da BPCO. Min Pneumol. 2014;53:1–6.
   Google Scholar
• Trabattoni D, Clerici M, Centanni S, et al. Immunomodulatory effects of pidotimod in adults with community-acquired pneumonia undergoing standard antibiotic therapy. Pulm Pharmacol Ther. 2017;44:24–29.
   PubMed Web of Science ®Google Scholar
• Clemente E, Solli R, Mei V, et al. Therapeutic efficacy and safety of pidotimod in the treatment of urinary tract infections in children. Arzneimittelforschung. 1994;44:1490–1494.
   PubMed Web of Science ®Google Scholar
• Li Y, Dai Y, Deng B, et al. Effect of pidotimod on interleukin-13 of patients with recurrent genital herpes. J Hainan Med Univ. 2011;17:1068–1070.
   Google Scholar
• Zhang C, Zhang W, Lin H. Effect of pidotimod on expressions of IL-2 and IL-10 of patients with genital herpes and curative effect observation. Chin J Pharmacoepidemiol. 2010;19:126–131.
   Google Scholar
• Guerra B, Perino A, Polatti F, et al. Pidotimod in the management of vulvar papillomatosis: double-blind clinical trial versus placebo. Am J Ther. 1998;5:147–152.
   PubMedGoogle Scholar
• Zervoudis S, Iatrakis G, Peitsidis P, et al. Complementary treatment with oral pidotimod plus vitamin C after laser vaporization for female genital warts: a prospective study. J Med Life. 2010;3:286–288.
   PubMedGoogle Scholar
• Wu Y, Ling J. Observation of impact and efficacy of Pidotimod on serum interleukin-4 and gamma-interferon levels in children with asthma. Chin Med Herl J. 2013;10:101–105.
   Google Scholar
• Jackson DJ, Hartert TV, Martinez FD, et al. Asthma: NHLBI workshop on the primary prevention of chronic lung diseases. Ann ATS. 2014;11(3):139–145.
   Google Scholar
• Caruso C, Buffa S, Candore G, et al. Mechanisms of immunosenescence. Immun Ageing. 2009;6:10.
   PubMedGoogle Scholar
• Meyer KC. The role of immunity and inflammation in lung senescence and susceptibility to infection in the elderly. Semin Respir Crit Care Med. 2010;31:561–574.
   PubMed Web of Science ®Google Scholar
• Niu H, Wang R, Jia Y-T, et al. Pidotimod, an immunostimulant in pediatric recurrent respiratory tract infections: a meta-analysis of randomized controlled trials. Int Immunopharmacol. 2019;67:35–45.
   PubMed Web of Science ®Google Scholar