64. A Series of Questions about the Antibiotic Doripenem.
The essay should answer these series of questions (each question should be answered in paragraph). the questions are:
1. The antibiotic doripenem (Doribax®) is recommended for use in patients with complicated urinary tract infections, including pyelonephritis.
Describe in detail what pyelonephritis is and the likely causative micro-organism(s)?
2. Describe the antimicrobial action of doripenem. Include in your answer details of bacterial resistance mechanisms towards this class of antimicrobials.
3. Describe the chemistry of doripenem (Doribax®) and explain how its structure confers antimicrobial activity. In comparison to amoxicillin, outline the unique chemical features of doripenem.
The New Delhi metallo-?-lactamase (NDM-1) from K. pneumoniae is highly efficient in the inactivation of doripenem. Briefly discuss the properties of NDM-1 and the mechanism of doripenem inactivation.
4. You are required to design a new doripenem analogue with antibacterial activity that is equivalent or comparable to doripenem. e-Draw the chemical structure of your doripenem analogue and provide a brief explanation of why your analogue would display clinically effective antibacterial activity.
5. Doripenem is currently only available for IV infusion. Assume you are working for a pharmaceutical company and have been tasked with designing an oral liquid formulation. Describe the process of designing this new formulation. Use referenced information on the physical and chemical properties of doripenem to justify your design decisions. If important properties are unknown, describe how you would experimentally obtain the information you need.
6. The table below lists pharmacokinetic parameters for doripenem in a healthy 70 kg individual:
Volume of distribution
16.8 L Total plasma clearance
15.9 L/h Plasma protein binding
8.1% Renal clearance
10.8 L/h Terminal half-life approx. 1 h
The recommended dosing regimen for treatment of complicated urinary tract infection is 500 mg by IV infusion over 1 hour, every 8 hours, for 10 days.
Using the data supplied, describe the disposition of doripenem over the course of the recommended regimen
7. Studies have reported that co-administration of doripenem with valproic acid results in a decrease in plasma concentration of valproic acid. What are the probable causes and consequences of this interaction?
8. In BNF 64, the monograph for Doribax® includes the symbol ?. What is this symbol? Why is this symbol in the monograph for Doribax®?
Include in your answer (a) a description of what the system represents and (b) what are its implications for clinical practice in the scenario?
Conclude your essay by providing a short summary of the key points you have highlighted above.
*use BNF 64 ,You must include a reference/bibliography list, in Harvard referencing style, at the end of the answers for each of the question