Absorption Of Ibuprofen Research Articles

Rapidly dissolving formulations for quick absorption during pain episodes: Ibuprofen

Pain or its associated trauma impairs oral absorption of drugs due, perhaps, to a diminished disintegration and dissolution rate secondary to suppression of the vagal nervous system. We first examined whether ibuprofen absorption is impaired on suppressing vagus nerve activity in a rat model. Secondly, we examined if ibuprofen absorption in rats during vagal suppression and in humans experiencing dental pain is improved by enhancing disintegration and dissolution rate of the administered formulation. Vagal suppression was achieved in rats by administering 20 mg/kg propantheline i.p. 2 h and 1 h before gastric gavage of 20 mg/kg ibuprofen as small crushed pieces of a regular release and a fast-dissolving ibuprofen caplets. In humans, after surgical removal of wisdom teeth and emergence of pain, 2 A 200 mg ibuprofen as regular released (n = 14) and fast-dissolving (n = 12) caplets were administered. Serial blood sample were collected for bioavailability studies. Vagal suppression resulted in significantly decreased absorption rate of ibuprofen enantiomers following administration of the regular release but not after fast-dissolving formulation. Human dental pain was associated with significantly slower absorption of ibuprofen enantiomers from the regular released as compared with the fast-dissolving caplets. Within the first hour post-dose the area under the plasma drug concentration-time curve was raised to 2.7-fold (p < 0.05) after the fast-dissolving as compared with the regular release formulations. There was a 1-h difference in the peak concentration time (tmax) between the two caplets. Impaired drug absorption appears to be due to slow disintegration and dissolution encountered during pain episodes.

Rationale for ibuprofen co-administration with antacids: Potential interaction mechanisms affecting drug absorption

Ibuprofen is a widely used NSAID which is often co-administered with antacids because of its gastro-irritant effects. Literature data suggest that antacid interactions may increase or decrease the drug’s absorption rate and onset of action and that the interaction may be formulation specific. In the present study, literature data on ibuprofen absorption were evaluated in order to gain insight into the nature of the in vivo effect. Solubility determinations in reactive media containing magnesium or aluminium and dissolution studies in the presence of antacid suspension were performed in an attempt to simulate in vitro the effects observed in vivo. The results obtained indicate that magnesium hydroxide enhances ibuprofen solubility, dissolution and bioavailability, while aluminium hydroxide has a retarding effect. Solubility studies indicated formation of a soluble solid ibuprofen phase in the presence of Mg 2+, in contrast, an insoluble ibuprofen salt was formed with Al 3+. The introduction of magnesium based antacid suspension into the dissolution media resulted in a formulation specific increase in drug dissolution rate with the most pronounced effect observed for the slowest release tablet formulation. The results obtained indicate the potential for in vitro studies to predict physicochemical interactions that are likely to influence drug absorption rate in vivo.

Effect of propylene glycol on ibuprofen absorption into human skin in vivo

The objective was to assess the impact of propylene glycol (PG), a common cosolvent in topical formulations, on the penetration of ibuprofen into human skin in vivo. Drug uptake into the stratum corneum (SC), following application of saturated formulations containing from 0 to 100% v/v PG, was assessed by tape-stripping. Dermatopharmacokinetic parameters, characterizing drug amount in and diffusivity through the SC, were derived. The solubility behavior of ibuprofen in PG-water mixtures was carefully evaluated, as were a number of other physical properties. Ibuprofen delivery depended on the level of PG in the vehicle, despite all formulations containing the drug at equal thermodynamic activity. PG appeared to alter the solubility of ibuprofen in the SC (presumably via its own uptake into the membrane), the effect becoming more important as the volume fraction of cosolvent in the formulation increased. In summary, tape-stripping experiments, with careful interpretation, can reveal details of a drug's bioavailability in the skin following topical application and may be used to probe the mechanism(s) by which certain excipients influence local drug delivery.

Enhanced Dissolution of Ibuprofen Using Solid Dispersion with Polyethylene Glycol 20000

To improve its dissolution, ibuprofen solid dispersions (SDs) were prepared in a relatively easy and simple manner, characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR), and evaluated for solubility and in vitro drug release. Loss of individual surface properties during melting and re-solidification as revealed by SEM micrographs indicated the formation of effective SDs. Absence or shifting toward the lower melting temperature of the drug peak in SDs in DSC study indicated the possibilities of drug–polymer interactions. FTIR spectra showed the presence of drug crystalline in SDs. The effect of improved dissolution on the oral absorption of ibuprofen in rats was also studied. Quicker release of ibuprofen from SDs in rat intestine resulted in a significant increase in AUC and Cmax, and a significant decrease in Tmax over pure ibuprofen. Preliminary results from this study suggested that the preparation of fast dissolving ibuprofen SDs by low-temperature melting method using polyethylene glycol 20000 as a meltable hydrophilic polymer carrier could be a promising approach to improve solubility, dissolution, and absorption rate of ibuprofen.

The Effect of Clove Oil on the Transdermal Delivery of Ibuprofen in the Rabbit by In Vitro and In Vivo Methods

The study was designed to evaluate skin permeation enhancement effect of essential oils from Eugenia caryophyllata (clove oil) in rabbits and to compare the in vitro absorption and in vivo permeation using ibuprofen as a model drug. The in vitro results indicated a significant permeation enhancement effect of the clove oil. The group with 1% oil appeared to the flux (239 μg/cm2/hr), and 3% oil was 293 μg/cm2/hr to some extent similar with 2% azone group (327 μg/cm2/hr). The enhancement ratio of clove oil was 7.3. In vivo results also demonstrated that clove oil showed a significant permeation enhancement effect, but the enhancement of clove oil was relatively weak than in vitro. The group with 3% oil exhibited the higher value of area under the curve (AUC) of 80.8 μg/mL·hr, which was 2.4 times the high of control. The AUC value of 3% oil group was similar to that of 2% azone group (89.8 μg/mL·hr). The GC-MS results indicated eugenol and acetyleugenol identified from clove oil might mainly contribute to enhance in vitro and in vivo absorption of ibuprofen because of its large quantities (90.93%).

Effect of intestinal fluid flux on ibuprofen absorption in the rat intestine

Previously the apparent permeability coefficient ( P app) of ibuprofen was observed to vary depending on the perfusion medium employed. The present work explores the possible contributions to these differences. Studies were undertaken using an in situ single pass rat gut technique. Lumenal drug concentrations and plasma drug levels were assayed by HPLC. Absorption rate constants ( k 0) were determined from fractions of drug unabsorbed from the intestineat steady state. Plasma data were fitted to a two compartment open model with zero-order input. Significant differences in net fluid flux were observed between the various buffered perfusion media, with fluxes varying from −0.044 ± 0.006 ml min −1 to +0.057 ± 0.013 ml min −1, the lower and negative values occurring for lower pH media and the larger positive values tending to occur with media of higher pH. A linear relationship was found between the P app of ibuprofen and net water flux ( y = 1.13 + 11.3 x; r 2 = 0.80). Apparent zero-order rate constants for ibuprofen appearance in plasma correlated well with absorption rate constants estimated from steady state lumenal drug concentration [ k 0(gut)]. From the linear relationship between P app and fluid flux a normalized P app for ibuprofen (i.e. the P app in the absence of net fluid flux) of 1.1 × 10 −4 cm s −1 was determined Net lumenal fluid flux is dependent on perfusion medium composition and significantly alters ibuprofen absorption. The differences observed for P app were reflected in systemic drug absorption concentrations. The findings of these studies underline the importance of standardizing the osmolarity of experimental media used for the determination of intestinal permeability data.

Perioperative pharmacokinetics of ibuprofen enantiomers after rectal administration

Ibuprofen is a nonsteroidal anti-inflammatory drug which has both peripheral and central analgesic effects. Ibuprofen has been shown to be an effective antipyretic and postoperative analgesic drug both in adults and children with few side effects. Pharmacokinetics of rectal ibuprofen has not been studied, although suppositories are frequently used for perioperative pain control in children. There were four study groups: full-term infants aged 1-7 weeks (n = 9), infants aged 8-25 weeks (n = 8), and infants aged 26-52 weeks (n = 7). Adult patients were 20-40 years old (n = 7). Ibuprofen suppository 20 mg.kg(-1) was administered after induction of anesthesia. Blood samples were collected from 20 min to 10 h after dosing and pharmacokinetic analysis of ibuprofen enantiomers were done. Both ibuprofen enantiomers were detectable in blood in 20 min. Total ibuprofen plasma concentrations >10 mg.l(-1) were seen from 40 min to 8 h. Values for T(max) of ibuprofen enantiomers and total ibuprofen were higher in the adult group than any of the infant groups (P < 0.05). In addition, values for physiological (standardized) t(1/2) of (R)-(-)- and (S)-(+)-ibuprofen were higher in infants aged 1-7 weeks than the adults (P < 0.05). None of the other pharmacokinetic variables, C(max), AUC, chronological t(1/2) or AUC ratio differed between the groups. A single dose of ibuprofen suppository 20 mg.kg(-1) after induction of anesthesia guarantees analgesic plasma concentrations during the early postoperative period. Except for the delayed absorption of ibuprofen in adults and higher physiological t(1/2) in infants aged 1-7 weeks, no major pharmacokinetic differences were observed between study groups.

Pharmacokinetic properties of combination oxycodone plus racemic ibuprofen: Two randomized, open-label, crossover studies in healthy adult volunteers

Background: As part of ongoing studies to evaluate the analgesic efficacy and pharmacokinetic properties of combination oxycodone plus ibuprofen in the treatment of moderate to severe acute pain, 2 pharmacokinetic studies were conducted. Objectives: The goals of these studies were to compare the pharmacokinetic properties of monotherapy with oxycodone or ibuprofen with those of a tablet formulation of these 2 agents combined (study A), and to determine whether the absorption of the individual agents when given in the combination tablet was affected by the concomitant ingestion of food (study B). Methods: Study A was a single-center, open-label, randomized, single-dose, 3-period, 3-way, crossover study Healthy male subjects received oxycodone 5 mg, ibuprofen 400 mg, or a combination tablet containing both, after an overnight fast of ≥8 hours, on study days 1, 8, and 15. Study B was a single-center, open-label, randomized, single-dose, single-crossover study. Healthy volunteers received a tablet containing a combination of oxycodone 5 mg plus ibuprofen 400 mg after either an overnight fast of ≥8 hours or a standardized high-fat breakfast. Both studies included a washout period of ≥7 days between treatments. In both studies, the pharmacokinetic properties (C max, T max, t 1/2, AUC 0-4, AUC 0-1, and AUC 0-∞) of oxycodone and ibuprofen were derived from plasma drug concentrations. Analysis of variance was used to determine and compare pharmacokinetic properties. Results: Twenty-four healthy, white, male subjects were included in study A (mean age, 26.0 years; mean body weight, 71.3 kg; mean height, 170.0 cm). Study B involved 12 subjects (11 men, 1 woman; mean age, 24.8 years; mean body weight, 77.2 kg; mean height, 181.4 cm). The pharmacokinetic properties of ibuprofen and oxycodone were not statistically different when administered alone or combined. Food intake did not affect the rate of oxycodone absorption (90% Cl of C max of fasted state vs fed state, 103–130), or the rate (90% Cl of C max of fasted state vs fed state, 72–95) or extent (90% Cl of AUC 0-∞ of fasted state vs fed state, 88–102) of ibuprofen absorption. The extent of oxycodone absorption was slightly increased when the combination was given with food (90% Cl of AUC 0-∞ of fasted state vs fed state, 115–127). Conclusions: The single-dose pharmacokinetic profiles of oxycodone and ibuprofen in these healthy volunteers were similar when these 2 drugs were given as monotherapy or in combination, suggesting bioequivalence. Food intake before administration of a single dose of the combination did not affect ibuprofen absorption but marginally increased the extent, but not the rate, of oxycodone absorption.

Ibuprofen Arginine for Primary Dysmenorrhea

Primary dysmenorrhea affects 40% to 70% of reproductive-aged women; its most likely cause is prostaglandins acting on uterine muscle. Prostaglandin-inhibiting nonsteroidal anti-inflammatory drugs are mainstays of treatment, but they have a slow onset of action. Combining the NSAID ibuprofen with arginine, a nitric-oxide synthesizer, accelerates the absorption of ibuprofen and might reduce gastric mucosal injury. These …

Citric acid as excipient in multiple-unit enteric-coated tablets for targeting drugs on the colon

Delivery of drugs to the large bowel has been extensively investigated during the last decade. The aim of this study was to investigate whether enteric-coated tablets could be made from enteric-coated matrix granules and drug release targeted to the colon. Whether in vitro drug release rate and in vivo absorption could be delayed by adding citric acid to the granules and/or to the tablet matrix was also studied. Ibuprofen was used as model drug because it is absorbed throughout the gastrointestinal tract. Eudragit™ S and Aqoat™ AS-HF were used as enteric polymers. Drug release rates were studied at different pH levels and drug absorption was studied in bioavailability tests. The conclusion was that citric acid retarded in vitro drug release when used in multiple-unit tablets. In vivo absorption of ibuprofen was markedly delayed when citric acid was included in both granules and tablet matrix. Further studies are needed to determine the optimal amount of citric acid in formulations.

Enteric polymers as binders and coating materials in multiple-unit site-specific drug delivery systems

The aim of this study was to develop a multiple-unit, site-specific drug formulation allowing targeting of drug release in the colon. Initially, characteristics of matrix pellets containing various enteric polymers as binders were tested. An enteric coating was then added to the formulations. Ibuprofen and furosemide were used as model drugs. The former is absorbed throughout the gastrointestinal tract, the latter only from upper parts. Methacrylate copolymers, hydroxypropyl methylcellulose acetate succinates and cellulose acetate phthalate were used as enteric polymers. The properties of the products were initially tested via dissolution studies at different pHs, then via bioavailability studies in healthy volunteers. The main conclusion was that drug release can be targeted on the distal part of the small intestine and the colon by preparing film-coated matrix pellets in which enteric polymers dissolving at pH≈7 have been used both as binders in the pellets and as coating material. This conclusion is based on the finding that absorption of ibuprofen from the formulations developed was adequate, with a lag-time of about 2 h and t max values at 4–5 h, where as absorption of furosemide from the analogous products was negligible. It was also found that uncoated pellets as such could represent a slow-release formulation for furosemide, a problem drug as far as modified-release products are concerned.

Clinical pharmacokinetics of ibuprofen. The first 30 years.

Ibuprofen is a chiral nonsteroidal anti-inflammatory drug (NSAID) of the 2 arylpropionic acid (2-APA) class. A common structural feature of 2-APANSAIDs is a sp3-hybridised tetrahedral chiral carbon atom within the propionic acid side chain moiety with the S-(+)-enantiomer possessing most of the beneficial anti-inflammatory activity. Ibuprofen demonstrates marked stereoselectivity in its pharmacokinetics. Substantial unidirectional inversion of the R-(-) to the S-(+) enantiomer occurs and thus, data generated using nonstereospecific assays may not be extrapolated to explain the disposition of the individual enantiomers. The absorption of ibuprofen is rapid and complete when given orally. The area under the plasma concentration-time curve (AUC) of ibuprofen is dose-dependent. Ibuprofen binds extensively, in a concentration-dependent manner, to plasma albumin. At doses greater than 600mg there is an increase in the unbound fraction of the drug, leading to an increased clearance of ibuprofen and a reduced AUC of the total drug. Substantial concentrations of ibuprofen are attained in synovial fluid, which is a proposed site of action for nonsteroidal anti-inflammatory drugs. Ibuprofen is eliminated following biotransformation to glucuronide conjugate metabolites that are excreted in urine, with little of the drug being eliminated unchanged. The excretion of conjugates may be tied to renal function and the accumulation of conjugates occurs in end-stage renal disease. Hepatic disease and cystic fibrosis can alter the disposition kinetics of ibuprofen. Ibuprofen is not excreted in substantial concentrations into breast milk. Significant drug interactions have been demonstrated for aspirin (acetylsalicylic acid), cholestyramine and methotrexate. A relationship between ibuprofen plasma concentrations and analgesic and antipyretic effects has been elucidated.

Antiulcer activities of liquorice and its derivatives in experimental gastric lesion induced by ibuprofen in rats

Ibuprofen is a clinically important non-steroidal anti-inflammatory analgesic and antipyretic drug widely used in the treatment of several forms of arthritis and for mild to moderate pain. Analogously to other aspirin-like drugs, ibuprofen irritates the gastric mucosa and liquorice extracts have long been used to treat peptic ulcers. In this study we examined the protective effect of liquorice or its derivatives against gastric ulcers induced by oral ibuprofen. A granular mixture of ibuprofen alone or coated with liquorice or its derivatives including deglycyrrhized liquorice (DGL), highly glycyrrhized liquorice (HGL), enoxolone (glycyrrhetinic acid) and carbenoxolone, were studied. Ibuprofen coated with liquorice, DGL or enoxolone reduced the number and size of ulcers, lowering the ulcer index from 1.86 to 1 and the incidence from 100 to 59%. Coating with other derivatives was less effective. Plasma concentrations of ibuprofen were determined by high-performance liquid chromatography (HPLC), and showed that ibuprofen absorption was not affected by liquorice or its derivatives.

Bioavailability of Racemic Ibuprofen and its Lysinate from Suppositories in Rabbits

Plasma concentration (C)–time (t) plots of ibuprofen from suppositories in rabbits are characterized by the sum of two exponentials, C = Be−λ2t – Ae−λ1t. When A exceeds B, there is a lag time (tlag= tc=0) before the start of absorption. Evidence for dose-dependent area under the curve (AUC) of C versus t values is presented with the implication that elimination rate constants (ke) decrease and the AUC/dose ratio increase with dose. The lack of significant differences between the AUC values from suppository and the intravenous studies with similar doses implies complete absorption of ibuprofen from all the suppositories studied. The absorption rate constants (ka) were estimated on the presumption of complete absorption and dose-dependent elimination. Ibuprofen lysinate was absorbed significantly more readily than the free acid from suppositories. The lysinate suppository with a lipophilic surfactant had a higher absorption rate constant than that with a hydrophilic surfactant. The ka values did not significantly differ for a twofold difference in dose. Equations were developed to calculate true AUC and area under the moment curve (AUMC) values when A exceeds B, and to transform C versus t plots to the origin with A’ = A = B. Times of maximum peak heights, mean residence (MRT), and mean absorption times (MAT = 1/ka of suppositories when A > B are shown to differ by the lag time (tc=0) from the plots of C versus t transposed to the origin. Although corrected AUC values when A > B are equal to the AUC values of C versus t plots transposed to the origin (A’ = A = B), the corrected AUMC values when A > B significantly differ from the AUMC values for the C versus t plots transposed to the origin.

Effect of age on ibuprofen pharmacokinetics and antipyretic response

The effect of age on ibuprofen pharmacokinetics and antipyretic effect was studied in 49 infants and children aged 3 months to 10.4 years. The relationship of plasma concentration to antipyretic effect was examined in 38 of the children by using an iterative least squares technique that allows estimation of drug concentration with time in a theoretical effect compartment and rate constant for elimination of drug from the effect compartment. There was a delay of 1 to 3 hours between peak ibuprofen plasma concentration and peak temperature decrement. The mean elimination rate constant from the effect compartment was 0.6 hour-1, corresponding to a half-life of drug in the effect compartment of 1.1 hours. The mean slope of the effect compartment concentration versus temperature regression line was -0.242 degrees C/mg per liter. Age did not significantly influence the rate of absorption of ibuprofen, its plasma concentration, its rate of elimination, or the time course of ibuprofen concentration in the effect compartment. However, in younger children the onset of antipyresis was earlier, maximum antipyretic effect was greater, and the area under the curve of the percentage of change in temperature from baseline versus time was greater than in older children. We conclude that the greater relative body surface area in younger children may allow more efficient dissipation of heat in response to antipyretic-induced lowering of the temperature "set point" in the hypothalamus.

The effect of magnesium hydroxide on the oral absorption of ibuprofen, ketoprofen and diclofenac.

1. The effect of magnesium hydroxide on the oral absorption of ibuprofen, ketoprofen and diclofenac was investigated in two randomized cross-over studies, both consisting of two phases. 2. Single doses of magnesium hydroxide (850 mg) or of water (150 ml) only were given to six healthy volunteers immediately after the ingestion of ibuprofen (400 mg, Study 1), ketoprofen (50 mg, Study 2) or diclofenac (50 mg, Study 2). Plasma drug concentrations were measured up to 24 h. 3. Magnesium hydroxide increased the area under the plasma ibuprofen concentration-time curve between 0 and 1 h by 65% (P less than 0.05) and the peak concentration of ibuprofen in plasma by 31% (P less than 0.01). The time to peak was shortened by about 0.5 h. The extent of bioavailability of ibuprofen was not increased by magnesium hydroxide. 4. Neither the rate nor the extent of absorption of ketoprofen or diclofenac was changed significantly by magnesium hydroxide. 5. When rapid onset of the analgesic effect of ibuprofen is required, concomitant ingestion of an antacid, which contains magnesium hydroxide without aluminium, is recommended.

Percutaneous absorption of ibuprofen and naproxen: Effect of amide enhancers on transport through rat skin

n-Alkanoic N, N-dimethylamides were found to act as penetration enhancers for the transport of ibuprofen and naproxen from suspensions in 50% aqueous propylene glycol vehicles across rat skin. Stripped skin and separated dermis were used to establish the maximum potential for enhancement and comparisons with established enhancers such as azone and N-methylpyrollidone were undertaken. Greatest enhancement was observed with naproxen but both drugs demonstrated a bell-shaped dependence on the alkyl chain length of the enhancer. Maximum effect was observed with N, N-dimethyloctanamide and N, N-dimethyldecanamide. Measurement of the skin-vehicle partition coefficients indicated that the partition of the drug into the skin was also maximal when these enhancers were incorporated into the vehicle. Permeation studies monitoring the flux of enhancer indicated that these compounds also penetrated the skin most effectively. In contrast, the enhancers had little effect on delivery from liquid paraffin vehicles.

Percutaneous absorption of ibuprofen: Vehicle effects on transport through rat skin

The transport of ibuprofen from propylene glycol vehicles through rat skin has been monitored in vitro. Skin stored for up to 4 months showed no significant change in its permeability to the drug but when the same tissue was used for consecutive experiments dramatic increases in flux were observed. Significant effects on drug permeation caused by vehicle composition and pH were found and solubilities and vehicle-skin partition coefficients were measured for all vehicles. As the concentration of propylene glycol increased permeation was related to the increase in solubility and reduction in partition coefficient. The pH effect was related to the degree of ionisation of the drug and to the effective concentration or degree of saturation when solutions were used. With suspensions of ibuprofen penetration rates were effectively independent of pH until high values were used when the vehicle interfered with the barrier properties of the skin.

The relationship between the pharmacokinetics of ibuprofen enantiomers and the dose of racemic ibuprofen in humans

Ibuprofen is a chiral drug which is used clinically as a racemate. The pharmacological properties of ibuprofen reside almost exclusively with the S(+)-enantiomer. However, a portion of R(-)-ibuprofen is metabolically inverted to its pharmacologically active, mirror-image form. To investigate the influence of increasing dose of racemic ibuprofen on the pharmacokinetics of its individual enantiomers, four healthy male volunteers were given racemic ibuprofen (200, 400, 800, and 1200 mg), orally, on four occasions. The study was conducted using a balanced cross-over design. The extent of absorption of ibuprofen, as assessed by the total urinary recovery of ibuprofen and its metabolites, was extensive and independent of the administered dose. At all four doses, the area under the total and unbound plasma concentration-time curves (AUC and AUCu, respectively), and the unbound fraction in plasma, were significantly greater for the S(+)-enantiomer. With increasing ibuprofen dose, there was a less than proportional increase in the AUC of each enantiomer, while the AUCu for both enantiomers increased in direct proportion to the administered dose. The time-averaged unbound fraction of each enantiomer increased significantly with increasing dose, which caused the non-linearity between AUC and dose. It was predicted that the metabolic intrinsic clearance of each enantiomer, and the fraction of R(-)-ibuprofen which was metabolically inverted to S(+)-ibuprofen, was independent of the administered dose.

Pharmacokinetics and absolute bioavailability of ibuprofen after oral administration of ibuprofen lysine in man

The lysine salt of d,l-2-(4-isobutylphenyl)-propionic acid (ibuprofen lysine) was administered as a single oral dose of 500 mg by means of commercially available coated tablets (Imbun).* To assess the absolute bioavailability of ibuprofen after its oral application as a lysine salt, intravenous injections of ibuprofen solutions containing 200 mg and 400 mg of the drug served as reference application. In a partially randomized cross-over design, 8 healthy male volunteers received three different single dose administrations which were separated by wash-out periods of 4 days each. Ibuprofen plasma concentrations were determined by HPLC using direct injection, pre-column enrichment and column switching techniques. From the results of intravenous injections one can deduce linear ibuprofen pharmacokinetics within the considered dosage range, with corresponding AUC0-infinity values of 3786 micrograms * min ml-1 and 7260 micrograms * min ml-1 for the 200 mg and 400 mg doses, respectively. The values of plasma clearances as well as those of different volumes of distribution showed remarkable constancy after evaluation from both intravenous injections. The absorption of orally administered ibuprofen lysine proved to be rapid, resulting in a mean peak plasma level (Cmax) of 31 micrograms ml-1 ibuprofen and in a mean time to peak (tmax) of 45 min. The absolute bioavailability of ibuprofen amounts to 102.7 per cent, indicating a complete absorption of ibuprofen when administered as its lysine salt. Drug tolerability was excellent for the oral administration of ibuprofen lysine as well as for the intravenous treatments with ibuprofen free acid. Only mild and transient adverse drug reactions such as mild burning or dragging sensation during injection or mild redness at the site of injection were reported.