Reviewer's report
Title:Early effects of oral administration of lafutidine with mosapride compared
with lafutidine alone on intragastric pH values
Version: 1Date:24 March 2009
Reviewer: Carmelo Scarpignato
Reviewer's report:
This is a straightforward paper dealing with a pharmacodynamic interaction
between a prokinetic compound (mosapride) and a novel H2-receptor antagonist
(H2RA), namely lafutidine.
Despite all the intrinsic limitations, there is still a place for H2RAs in the era of
PPIs. Besides controlling NAB (i.e. Nocturnal Acid Breakthrough), often observed
even with twice daily PPIs, H2RAs (especially soluble or OTC formulations) will
become the “antacids of the third millennium” and will be particularly useful for
on-demand symptom relief. The onset of the antisecretory will then be
particularly important. In this connection, this work is a welcome one since it does
give an additional rationale for adding a prokinetic agent to an antisecretory
compound. Indeed, in GERD this combination (usually with a PPI) has been
adopted to increase gastric emptying rate (often delayed in a significant
proportion of patients), thus reducing in that way the amount of gastric contenta
available for reflux. Yet, another good reason could be to speed up the intestinal
absorption of the antisecretory compound (be it a PPI or an H2RA) and achieve a
quicker increase of intragastric pH, with consequent quicker symptom control.
This pharmacodynamic study clearly shows that this is the case. The paper is
well written, the methodology is simple and correct, data are presented and
discussed clearly.
It is not stated whether the subjects under investigation were fed or (as I guess)
fasted. A similar experiment in fed subjects, measuring also post-prandial
intra-esophageal pH, could be particularly useful to evaluate the effect of this
drug combination on esophageal exposure to acid.
In addition, I am sure blood samples have been collected during the study. If this
is the case, the investigators should measure lafutidine pharmacokinetics and
quantitate the relevant PK parameters (Cmax, Tmax, AUC, etc) to give the
readers a better insight into the clinical relevance of this drug combination.
The authors should also discuss the potential clinical utility of a fixed
mosapride-lafutidine combination, where a specifically developed formulation
could assure a sequential release of the different compounds.
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests
Reviewer's report
Title:Early effects of oral administration of lafutidine with mosapride compared
with lafutidine alone on intragastric pH values
Version: 1Date:24 March 2009
Reviewer: Carmelo Scarpignato
Reviewer's report:
This is a straightforward paper dealing with a pharmacodynamic interaction
between a prokinetic compound (mosapride) and a novel H2-receptor antagonist
(H2RA), namely lafutidine.
Despite all the intrinsic limitations, there is still a place for H2RAs in the era of
PPIs. Besides controlling NAB (i.e. Nocturnal Acid Breakthrough), often observed
even with twice daily PPIs, H2RAs (especially soluble or OTC formulations) will
become the “antacids of the third millennium” and will be particularly useful for
on-demand symptom relief. The onset of the antisecretory will then be
particularly important. In this connection, this work is a welcome one since it does
give an additional rationale for adding a prokinetic agent to an antisecretory
compound. Indeed, in GERD this combination (usually with a PPI) has been
adopted to increase gastric emptying rate (often delayed in a significant
proportion of patients), thus reducing in that way the amount of gastric contenta
available for reflux. Yet, another good reason could be to speed up the intestinal
absorption of the antisecretory compound (be it a PPI or an H2RA) and achieve a
quicker increase of intragastric pH, with consequent quicker symptom control.
This pharmacodynamic study clearly shows that this is the case. The paper is
well written, the methodology is simple and correct, data are presented and
discussed clearly.
It is not stated whether the subjects under investigation were fed or (as I guess)
fasted. A similar experiment in fed subjects, measuring also post-prandial
intra-esophageal pH, could be particularly useful to evaluate the effect of this
drug combination on esophageal exposure to acid.
In addition, I am sure blood samples have been collected during the study. If this
is the case, the investigators should measure lafutidine pharmacokinetics and
quantitate the relevant PK parameters (Cmax, Tmax, AUC, etc) to give the
readers a better insight into the clinical relevance of this drug combination.
The authors should also discuss the potential clinical utility of a fixed
mosapride-lafutidine combination, where a specifically developed formulation
could assure a sequential release of the different compounds.
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests
Please review this paper.
user
Reviewer's report
Title:Early effects of oral administration of lafutidine with mosapride compared
with lafutidine alone on intragastric pH values
Version: 1Date:24 March 2009
Reviewer: Carmelo Scarpignato
Reviewer's report:
This is a straightforward paper dealing with a pharmacodynamic interaction
between a prokinetic compound (mosapride) and a novel H2-receptor antagonist
(H2RA), namely lafutidine.
Despite all the intrinsic limitations, there is still a place for H2RAs in the era of
PPIs. Besides controlling NAB (i.e. Nocturnal Acid Breakthrough), often observed
even with twice daily PPIs, H2RAs (especially soluble or OTC formulations) will
become the “antacids of the third millennium” and will be particularly useful for
on-demand symptom relief. The onset of the antisecretory will then be
particularly important. In this connection, this work is a welcome one since it does
give an additional rationale for adding a prokinetic agent to an antisecretory
compound. Indeed, in GERD this combination (usually with a PPI) has been
adopted to increase gastric emptying rate (often delayed in a significant
proportion of patients), thus reducing in that way the amount of gastric contenta
available for reflux. Yet, another good reason could be to speed up the intestinal
absorption of the antisecretory compound (be it a PPI or an H2RA) and achieve a
quicker increase of intragastric pH, with consequent quicker symptom control.
This pharmacodynamic study clearly shows that this is the case. The paper is
well written, the methodology is simple and correct, data are presented and
discussed clearly.
It is not stated whether the subjects under investigation were fed or (as I guess)
fasted. A similar experiment in fed subjects, measuring also post-prandial
intra-esophageal pH, could be particularly useful to evaluate the effect of this
drug combination on esophageal exposure to acid.
In addition, I am sure blood samples have been collected during the study. If this
is the case, the investigators should measure lafutidine pharmacokinetics and
quantitate the relevant PK parameters (Cmax, Tmax, AUC, etc) to give the
readers a better insight into the clinical relevance of this drug combination.
The authors should also discuss the potential clinical utility of a fixed
mosapride-lafutidine combination, where a specifically developed formulation
could assure a sequential release of the different compounds.
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests
assistant