Herb-drug interaction of Andrographis paniculata (Nees) extract and andrographolide on pharmacokinetic and pharmacodynamic of naproxen in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Andrographis paniculata Nees (Acanthacae) have broad range of pharmacological effects such as hepatoprotective, antifertility, antimalarial, antidiabetic, suppression of various cancer cells and anti-inflammatory properties and is widely used medicinal plant in the traditional Unani and Ayurvedic medicinal systems. Andrographolide (AN) is one of the active constituent of the A. paniculata Nees extract (APE). They have been found in many traditional herbal formulations in India and proven to be effective as anti-inflammatory drug. AIM OF THE STUDY: To evaluate the pharmacokinetic and pharmacodynamic (anti arthritic) herb-drug interactions of A. paniculata Nees extract (APE) and pure andrographolide (AN) with naproxen (NP) after oral co-administration in wistar rats. MATERIALS AND METHODS: After oral co-administration of APE (200mg/Kg) and AN (60mg/kg) with NP (7.5mg/kg) in rats, drug concentrations in plasma were determined using HPLC method. The main pharmacokinetic parameters of Cmax, tmax, t1/2, MRT, Vd, CL, and AUC were calculated by non-compartment model. Change in paw volume, mechanical nociceptive threshold, mechanical hyperalgesia, histopathology and hematological parameters were evaluated to study antiarthritic activity. RESULTS: Co-administration of NP with APE and pure AN decreased systemic exposure level of NP in vivo. The Cmax, tmax, AUC0-t of NP was decreased. In pharmacodynamic study, NP (10mg/kg) alone and NP+AN (10+60mg/kg) groups exhibited significant synergistic anti-arthritic activity as compared to groups NP+APE, APE and AN alone. CONCLUSION: The results obtained from this study suggested that NP, APE and pure AN existed pharmacokinetic herb-drug interactions in rat which is correlated with anti-arthritic study. The knowledge regarding possible herb-drug interaction of NP might be helpful for physicians as well as patients using AP. So further studies should be done to understand the effect of other herbal ingredients of APE on NP as well as to predict the herb-drug interaction in humans.

Measurement of plasma ibuprofen by gas chromatography-mass spectrometry.

A gas-chromatography-mass spectrometry (GC-MS) method for the determination of plasma ibuprofen was developed. Plasma samples from cystic fibrosis (CF) patients receiving high-dose ibuprofen therapy were analyzed by GC-MS and the result compared to analysis by high-performance liquid chromatography (reference method). Analysis of ibuprofen was sensitive to at least 5 mg/L, and the method was linear to 200 mg/L. Within-run variations of plasma samples were 4.6% (131.7 +/- 6.0 mg/L) and 5.4% (44.4 +/- 2.4 mg/L), respectively. The between-run variation was 9.3% (45.4 +/- 4.2 mg/L) and 7.4% (88.0 +/- 6.5 mg/L). This method is suited for routine clinical use for the monitoring of plasma ibuprofen levels in treatment of CF. It may be particularly applicable in pediatric laboratories, which are likely to possess GC-MS capability.

[The modification of the pharmacokinetics and analgesic effect of naproxen by cimetidine, phenobarbital and thiamine diphosphate]. / Modifikatsiia farmakokinetiki i anal'geticheskogo éffekta naproksena tsimetidinom, fenobarbitalom i tiamindisfosfatom.

Phenobarbital in a dose of 70 mg/kg (one-time daily intraperitoneal administration for 5 days) promotes naproxen elimination from rat blood and reduces its analgesic activity. Cymetidine (intragastric one-time daily administration in a dose of 100 mg/kg for a week) inhibits naproxen elimination from blood and increases it analgesic effect. Thiamine diphosphate administered intraperitoneally in a dose of 10 mg/kg (one time a day for a week) does not change pharmacokinetic and analgesic effect of naproxene.

Usefulness of the pain-induced functional impairment model to relate plasma levels of analgesics to their efficacy in rats.

In this work we show that the pain-induced functional impairment model (PIFIR) can be used with cannulated rats as a useful procedure for pharmacokinetic/pharmacodynamic modelling. This model evaluates analgesia by measuring motor impairment of the right limb after intra-articular administration of uric acid. Time of contact with a rotating cylinder is referred to the control limb. We studied the pharmacokinetic and pharmacodynamics of naproxen after six peroral doses to Wistar rats, and we examined the adjuvant action of caffeine with naproxen. Surgery and blood sampling did not produce any difference on functional impairment either in rats without uric acid or in the dysfunction produced by uric acid. The relation between naproxen plasma concentration and the analgesic effect was obtained with few rats. Caffeine alone did not produce any significant modification in functional impairment but the co-administration significantly increased the effect of naproxen. Plasma levels of naproxen did not change when caffeine was co-administered. The PIFIR model with blood sampling is a suitable method for pharmacokinetic/pharmacodynamic relationship studies and is specially useful to characterize drug-drug interactions.