Pharmacokinetic Evaluation of Risperidone and Its Active Metabolite When Risperidone Oral Solution Is Mixed with Black Tea in Rats

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The authors provide interesting results.

Comparison of the concentrations at each data point statistically can demonstrate that the shape of the concentration-time curve changes substantially.

In addition, it would also be interesting to see the effects on the sum of risperidone and its active metabolite (active moiety), because it is believed that the active moiety correlates better with the effect than risperidone concentrations.

A table comparing the values for the active moiety would also be useful.

Figures: error bars should also be shown for the semilogarithmic plots. The points can be connected with a dotted line to show the difference in the shape of the curves.

 

Author Response

We would like to thank the reviewers for their valuable comments and suggestions.
We have carefully revised the manuscript accordingly and addressed all comments point-by-point in the response letter.
In addition, a new graphical abstract has been prepared and included in the revised submission.

Author Response File: Author Response.docx

Reviewer 2 Report

Comments and Suggestions for Authors

The manuscript is interesting but few points need to be considered.

1. The chromatographic method sensitivity is not described. What was the LLOQ?
2. Please also give the low QC, medium QC, and high QC concentrations.
3. It will be better to provide the representative chromatograms of the method.
4. Were short term and long-term stabilities of the spiked samples performed? Please provide brief information regarding sample stability and storage conditions.
5. Line 313-314, the concentrations for both RIS and 9-OH-RIS are same. If the blood concentrations in animal models for both analytes are at same level then it is fine but if it varies then the concentration levels need to be different. Furthermore, why high concentrations upto 1000 ng/ml has been used. The upper limit should have been around 200 ng/ml
6. Some information needs to be provided regarding the composition of Dimbula tea and is there any differences between the constituents (chemical composition) of Dimbula tea and other tea.
7. Create line charts (adding line) to the concentration vs time graphs for easy interpretation of the graphs.
8. Usually, drug metabolite ratios are also described in pharmacokinetic interactions. Is it possible to add this?
9. In table 2, the difference in tmax between the two groups is high but the difference is non-significant. Please check and verify the values.
10. The manuscript needs to be carefully read and evaluated for English e.g. line 251 “Wister”
11. Most of the studies on tea have been performed by Japanese. Most of the references in this study are also of Japanese origin. It is requested to increase the number of references and add studies of other than Japanese origin. It may also include reported pharmacokinetic interactions of risperidone.

Author Response

We would like to thank the reviewers for their valuable comments and suggestions.
We have carefully revised the manuscript accordingly and addressed all comments point-by-point in the response letter.
In addition, a new graphical abstract has been prepared and included in the revised submission.

Author Response File: Author Response.docx

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

The authors have improved the manuscript. However, line 404 need correction."QC samples were prepared at 8.00, 80.0, and 800 ng/mL as low-, medium-, and high
QC samples, respectively". The medium QC is too low, according to ICH guidelines it should be around 30 - 50% of the calibration curve's working range.

Author Response

Please see the attachment.

Author Response File: Author Response.docx