Analgesic eluting bone cement: A novel approach for targeted pain management in total knee arthroplasty - An in-vitro study.

BACKGROUND: The average rate of patient dissatisfaction following total knee arthroplasty (TKA) is 10%. Multi-modal analgesia is the present standard of pain management after TKA. Studies show that with multi-modal analgesia, approximately 60% of patients experience severe knee pain following surgery, while around 30% experience moderate pain. To date, there is no literature available on targeted pain management using bone cement. OBJECTIVES: To investigate the feasibility of incorporating anti-inflammatory medications and identify the analgesic with the best release pharmacokinetics from bone cement for application in pain management. METHODS: In an in-vitro study, 100 mg of five drugs (aceclofenac, diclofenac, naproxen, paracetamol and methyl prednisolone) were incorporated into bone cement (Palacos). Cement cubes holding each drug were made and allowed to harden for 30 min. Each drug-containing cube was placed in a beaker with saline for 72 h. Fractions of 10 ml were collected at 0, 6, 24, 48 and 72 h and analysed using high-pressure liquid chromatography to measure the percentage release of the drug from bone cement. RESULTS: Naproxen showed superior elution from bone cement, with 10.9% at 24 h and 9.08% at 72 h. Paracetamol showed 4.9% at 24 h and 3.78% at 72 h, aceclofenac 0.2% at 24 h and 0.4% at 72 h, diclofenac 3.03% at 24 h and 1.99% at 72 h, and methylprednisolone 0.26% at 24 h and 0.32% at 72 h. CONCLUSIONS: Polymethylmethacrylate bone cement can elute analgesics in vitro. Among the five drugs studied, naproxen had the best release kinematics from polymethylmethacrylate bone cement. Analgesic eluting bone cement is a novel approach for targeted postoperative pain management in TKA.

Assessment of Pharmacodynamic and Pharmacokinetic Interaction of Aqueous Extract of Cassia auriculata L. and Metformin in Rats.

BACKGROUND: Cassia auriculata L. (CA) leaf extract might increase the body's production of insulin thereby suppressing the elevated blood glucose and lipid levels in diabetic rats. CA has been used as dietary supplement in India from ancient times. OBJECTIVE: The present study was to elucidate the synergistic pharmacodynamic (PD) and pharmacokinetic (PK) interaction of metformin (MT) with CA. MATERIALS AND METHODS: A simple, precise reverse phase high performance liquid chromatography - UV detection mode method was developed to quantify MT in rat plasma. In PD interaction, streptozotocin (45mg/kg, intraperitoneally) induced diabetic Wistar rats weighing 180-250 g of either sex were randomized to receive MT (90 mg/kg, MT-HD), CA (500 mg/kg) separately and in combination of MT (90 mg/kg, MT-HD) + CA (500 mg/kg), and MT (45 mg/kg, MT-LD) + CA (500 mg/kg) (all oral) along with normal and diabetic control groups for 21 days. PK of MT was carried out in normal rats with preadministration of CA (500 mg/kg) for 14 days. RESULTS: PD data showed reasonable blood glucose lowering effect of CA. The reduction of MT dose with combination of CA achieved a similar blood glucose lowering effect of MT alone. PK data showed enhanced time taken to achieve maximum plasma concentration (Cmax), area under the curve (AUC0-t), and Cmax in combination group of MT (90mg/kg) and CA (500mg/kg), and reduction of MT dose in Group III had a reduced Cmax and AUC0-t compared to MT alone treated groups. CONCLUSION: Co-administration of CA with MT at varying dose showed a synergistic herb-drug interaction. Thus using the synergistic herb-drug interaction, the dose level of MT may be reduced to produce the same therapeutic effect as when taken alone. SUMMARY: Elucidating the synergistic pharmacodynamic (PD) and pharmacokinetic (PK) interaction of metformin (MT) with Cassia auriculata L. (CA)PD data showed reasonable blood glucose lowering effect of CA. The reduction of MT dose with combination of CA achieved a similar blood glucose lowering effect of MT alonePK data showed enhanced time taken to achieve maximum plasma concentration (Cmax), area under the curve (AUC0-t), and Cmax in combination group of MT and CA, and reduction of MT dose had a reduced Cmax and AUC0-t compared to MT alone treated groupsCo-administration of CA with MT at varying dose showed a synergistic herb-drug interaction. Thus using the synergistic herb-drug interaction, the dose level of MT may be reduced to produce the same therapeutic effect as when taken alone. Abbreviations used: CA: Cassia auriculata L., PD: Pharmacodynamic, PK: Pharmacokinetic, MT: Metformin, RP-HPLC-UV: Reverse phase High Performance Liquid Chromatography-UV detection mode, Tmax: Time taken to achieve maximum plasma concentration, AUC0-t: Area under the curve, Cmax: Maximum plasma concentration.