Is Individualization of Sodium Bicarbonate Ingestion Based on Time to Peak Necessary?

PURPOSE: To describe the reliability of blood bicarbonate pharmacokinetics in response to sodium bicarbonate (SB) supplementation across multiple occasions and assess, using putative thresholds, whether individual variation indicated a need for individualized ingestion timings. METHODS: Thirteen men (age 27 ± 5 yr; body mass [BM], 77.4 ± 10.5 kg; height, 1.75 ± 0.06 m) ingested 0.3 g·kg BM SB in gelatine capsules on three occasions. One hour after a standardized meal, venous blood was obtained before and every 10 min after ingestion for 3 h, then every 20 min for a further hour. Time to peak (Tmax), absolute peak (Cmax), absolute peak change ([INCREMENT]Cmax), and area under the curve were analyzed using mixed models, intraclass correlation coefficient, coefficient of variation and typical error. Individual variation in pharmacokinetic responses was assessed using Bayesian simulation with multilevel models with random intercepts. RESULTS: No significant differences between sessions were shown for blood bicarbonate regarding Cmax, [INCREMENT]Cmax or area under the curve (P > 0.05), although Tmax occurred earlier in SB2 (127 ± 36 min) than in SB1 (169 ± 54 min, P = 0.0088) and SB3 (159 ± 42 min, P = 0.05). Intraclass correlation coefficient, coefficient of variation, and typical error showed moderate to poor reliability. Bayesian modeling estimated that >80% of individuals from the population experience elevated blood bicarbonate levels above +5 mmol·L between 75 and 240 min after ingestion, and between 90 and 225 min above +6 mmol·L. CONCLUSIONS: Assessing SB supplementation using discrete values showed only moderate reliability at the group level, and poor reliability at the individual level, whereas Tmax was not reproducible. However, when analyzed as modeled curves, a 0.3-g·kg BM dose was shown to create a long-lasting window of ergogenic potential, challenging the notion that SB ingestion individualized to time-to-peak is a necessary strategy, at least when SB is ingested in capsules.

Effect of stearic acid on the properties of metronidazole/methocel K4M floating matrices / Efeito do ácido esteárico nas propriedades de metronidazol / Methocel K4M matrizes flutuante

The properties of metronidazole/Methocel K4M sustained release floating tablets have been studied varying the proportion of the lubricant, stearic acid, on formulations with and without sodium bicarbonate. The variables studied include technological properties of the tablets such as tablet hardness and ejection pressure, the drug release profile, the hydration kinetics and the floating behaviour. The presence of stearic acid and sodium bicarbonate improves the floating behaviour for more than 8 hours. The hydration volume, the tablet hardness and the ejection pressure decrease as the stearic acid content increases and the polymer content decreases. Drug dissolution increases with increasing proportions of stearic acid and decreasing proportions of the polymer in the tablets. The presence of sodium bicarbonate extends the differences in dissolution produced by stearic acid. These results are attributed to decreasing matrices coherence with an increasing quantity of stearic acid and a reducing polymer proportion. The carbon dioxide bubbles produced by sodium bicarbonate expand the matrices facilitating the dissolution, although their presence obstructs also the diffusion path through the hydrated gel layer.

Estudaram-se as propriedades de comprimidos flutuantes de metronidazol/Methocel K4M de liberação controlada, variando-se a proporção do lubrificante, ácido esteárico, nas formulações com e sem bicarbonato de sódio. As variáveis estudadas incluem propriedades tecnológicas dos comprimidos, tais como dureza, pressão de ejeção, perfil de liberação do fármaco, cinética de hidratação e comportamento de flutuação. A presença de ácido esteárico e do bicarbonato de sódio melhora o comportamento de flutuação para mais de 8 horas. O volume de hidratação, a dureza e a pressão de ejeção do comprimido decrescem à medida que o conteúdo de ácido esteárico e de polímero diminui. A dissolução do fármaco aumenta com o aumento das proporções de ácido esteárico e a diminuição das proporções de polímero nos comprimidos. A presença de bicarbonato de sódio amplia as diferenças na dissolução produzidas pelo ácido esteárico. Estes resultados são atribuídos à coesão decrescente das matrizes, com o aumento da quantidade de ácido esteárico e a redução da proporção de polímero. Bolhas de dióxido de carbono produzidas pelo bicarbonato de sódio expandem as matrizes, facilitando a dissolução, embora a presença delas obstrua, também, a difusão através da camada de gel hidratado.

Relative bioavailability of new formulation of paracetamol effervescent powder containing sodium bicarbonate versus paracetamol tablets: a comparative pharmacokinetic study in fed subjects.

OBJECTIVE: the aim of this relative bioavailability study was to determine the rate and extent of absorption of Alikal Dolor (effervescent powder containing paracetamol 500 mg/sodium bicarbonate 2318 mg)--test formulation (T) in relation to Parageniol (paracetamol 500 mg coated tablets)--reference formulation (R). METHODS: 18 healthy volunteers (10 male and 8 female aged between 21 and 46 years) received, after 2 h of standardized breakfast, a single oral dose with 220 ml of water, in an open, randomized, crossover study, with a 7-day wash-out period. Paracetamol concentrations were established at 0, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 75, 90 min and at 2, 4, 6, 8 and 10 h postdose by HPLC with an ultraviolet detector. RESULTS: the regression coefficient determined for paracetamol calibration curves was 0.9983 +/- 0.0034 and the working range was from 0.2 to 50 microg/ml. The quantification limit was 0.2 microg/ml. The rate of absorption was significantly greater (p < 0.03) for T (T(max) = 20.4 min) compared with R (T(max) = 38.4 min). Extent of absorption over the first 30 min postdose AUC((0-30 min)) was 4.21-fold greater (p < 0.03) for T compared with R, without differences between C(max.) The 90% CI on the geometric mean for C(max), AUC((0-10 h)) and AUC((0-)) ratios (T/R) were within the limits of 0.80-1.25, indicating both formulations were bioequivalent with respect to these parameters. CONCLUSION: paracetamol was absorbed at least twice as fast from T-containing sodium bicarbonate compared with R. This pharmacokinetic feature could prove crucial from the therapeutic point of view as it would allow a lower latency in the action time of paracetamol in producing its analgesic and antithermal effect.

Apparent bicarbonate space in children.

The amount needed to change the concentration of a solute requires the knowledge of its volume of distribution in the solution. Electrolytes that do not participate in active metabolic reactions have a fixed volume of distribution that corresponds to the volume of water in which they solubilize. Bicarbonate infusion is used to correct hyperchloremic metabolic acidosis. Its volume of distribution (bicarbonate space) changes with its participation in the blood buffer systems. In other words, it is not a fixed physical volume, like that of other solutes. In this paper, we shall review experimental studies that supported evidence for this knowledge and analyze the basic hypothesis to explain the phenomena. Since we have not found clinical studies in children, we shall report our experience in a group of patients with metabolic acidosis treated with bicarbonate infusion in whom apparent bicarbonate space was measured and compared with data in adults from the literature. Guidelines for amount of bicarbonate needed to increase its concentration according to baseline bicarbonate concentration will be suggested.