PMID- 29467656
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 9
DP  - 2018
TI  - Sublingual Administration of Sildenafil Oro-dispersible Film: New Profiles of 
      Drug Tolerability and Pharmacokinetics for PDE5 Inhibitors.
PG  - 59
LID - 10.3389/fphar.2018.00059 [doi]
LID - 59
AB  - Objective: Type 5 phosphodiesterase inhibitors (PDE5i) are efficient drugs used 
      for treatment of erectile dysfunction (ED); however, a large discontinuation rate 
      due to major side effects is reported. The aim of this study was to evaluate the 
      possible improvement of sildenafil (Sild) pharmacokinetics associated to the 
      sublingual administration of the new available oro-dispersible film (ODF), 
      compared to both the oro-dispersible tablet (ODT) and the film-coated tablet 
      (FCT) as original per os formulation. Methods:In vitro disaggregation test, 
      dissolution test, and permeation test in specific devices to estimate the 
      trans-mucosal absorption. In vivo analysis of serum Sild levels, by high 
      performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), was 
      performed in 20 patients with psychogenic ED receiving alternatively per os FCT 
      or sublingual ODT or ODF, at an equal dosage (50 mg). Pharmacokinetic parameters 
      of Sild and adverse drug reactions experienced after the dosing of each 
      formulation were compared. Results:In vitro, ODF showed the highest time to 
      disaggregation and an increased rate of permeation compared to both ODT and FCT 
      (P = 0.017 and P = 0.008, respectively). In vivo, compared to both FCT and ODT, 
      ODF showed a faster increase of serum Sild levels (serum levels at 15 min from 
      dosing, respectively: 2.24 +/- 1.4 ng/ml FCT, 0.5 +/- 0.3 ng/ml ODT, and 13.5 +/- 9.1 
      ng/ml ODF; P < 0.01 and P < 0.05 vs. ODF) together with a higher drug 
      bioavailability within 60 min from dosing (relative AUC(60)(min) vs. FCT, 
      respectively: 100.0 +/- 44.9% FCT, 183.8 +/- 75.4% ODT, and 304.2 +/- 156.0% ODF). A 
      trend toward lower peak serum levels was observed for ODF. Finally, ODF showed a 
      lower prevalence of headache compared to FCT (1 vs. 35%; P < 0.05) and improved 
      pattern of flushing and nasal congestion. Conclusion: Sublingual Sild ODF 
      improves the drug tolerability through a likely modified pharmacokinetic, 
      suggesting a possible implication also in the clinical efficacy profile. 
      Sublingual administration of oro-dispersible formulations may represent a 
      strategy to ameliorate the adherence to therapy with PDE5i, particularly in 
      patients discouraged by side effects.
FAU - De Toni, Luca
AU  - De Toni L
AD  - Department of Medicine, Unit of Andrology and Reproductive Medicine, University 
      of Padova, Padova, Italy.
FAU - De Rocco Ponce, Maurizio
AU  - De Rocco Ponce M
AD  - Department of Medicine, Unit of Andrology and Reproductive Medicine, University 
      of Padova, Padova, Italy.
FAU - Franceschinis, Erica
AU  - Franceschinis E
AD  - PharmaTeG - Pharmaceutical Technology Group, Department of Pharmaceutical and 
      Pharmacological Sciences, School of Medicine, University of Padova, Padova, 
      Italy.
FAU - Dall'Acqua, Stefano
AU  - Dall'Acqua S
AD  - Department of Pharmaceutical and Pharmacological Sciences, School of Medicine, 
      University of Padova, Padova, Italy.
FAU - Padrini, Roberto
AU  - Padrini R
AD  - Clinical Pharmacology Unit, Department of Medicine, School of Medicine, 
      University of Padova, Padova, Italy.
FAU - Realdon, Nicola
AU  - Realdon N
AD  - PharmaTeG - Pharmaceutical Technology Group, Department of Pharmaceutical and 
      Pharmacological Sciences, School of Medicine, University of Padova, Padova, 
      Italy.
FAU - Garolla, Andrea
AU  - Garolla A
AD  - Department of Medicine, Unit of Andrology and Reproductive Medicine, University 
      of Padova, Padova, Italy.
FAU - Foresta, Carlo
AU  - Foresta C
AD  - Department of Medicine, Unit of Andrology and Reproductive Medicine, University 
      of Padova, Padova, Italy.
LA  - eng
PT  - Journal Article
DEP - 20180206
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC5808105
OTO - NOTNLM
OT  - PDE5 inhibitors
OT  - adverse drug reaction
OT  - drug formulation
OT  - erectile dysfunction
OT  - sublingual route
EDAT- 2018/02/23 06:00
MHDA- 2018/02/23 06:01
PMCR- 2018/02/06
CRDT- 2018/02/23 06:00
PHST- 2017/12/07 00:00 [received]
PHST- 2018/01/17 00:00 [accepted]
PHST- 2018/02/23 06:00 [entrez]
PHST- 2018/02/23 06:00 [pubmed]
PHST- 2018/02/23 06:01 [medline]
PHST- 2018/02/06 00:00 [pmc-release]
AID - 10.3389/fphar.2018.00059 [doi]
PST - epublish
SO  - Front Pharmacol. 2018 Feb 6;9:59. doi: 10.3389/fphar.2018.00059. eCollection 
      2018.