Steady‐State Lithium Blood Level Fluctuations in Man Following Administration of a Lithium Carbonate Conventional and Controlled‐Release Dosage Form

Caldwell, Henry C.; Westlake, Wilfred J.; Schriver, Robert C.; Bumbier, Edgar E.

doi:10.1002/j.1552-4604.1981.tb01758.x

Cited by 17 publications

(5 citation statements)

References 5 publications

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“…Average TPM plasma concentration during dosing interval at steady state (C avg ) was calculated from the quotient of AUC 0–24 /τ. FI of TPM plasma concentration was calculated using eqn , where trough concentration (C min ) was determined as the minimum observed concentration after dosing of TPM‐IR or USL255 (Caldwell et al., ; Silber et al., ):

FI = \frac{C_{\max} ‐ C_{\min}}{C_{avg}}

…”

Section: Methodsmentioning

confidence: 99%

“…The major PK parameters used to assess rate of absorption (e.g., C max and t max [time to C max ]) are not ideal in cases of flat concentration‐time curves obtained after oral dosing of ER formulations such as USL255 (Lambrecht et al., ). Therefore, multiple PK parameters were evaluated to assess steady‐state performance of USL255 compared with TPM‐IR in vivo, which included both standard parameters (i.e., AUC 0–24 [AUC at steady state], C max , C min , C avg [average TPM plasma concentration at steady state], t max ) and less common PK criteria – FI, peak occupancy or plateau time (POT), and percent coefficient of variation of the TPM steady‐state plasma concentration (%CV) – that estimate the flatness of the TPM plasma concentration‐time curves (Caldwell et al., ; Silber et al., ; Pollak et al., ; Bialer et al., ). In addition, comparative analyses using the metric partial area under the concentration–time curve (AUC p ) were conducted on TPM steady‐state PK data.…”

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confidence: 99%

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Comparative steady‐state pharmacokinetic evaluation of immediate‐release topiramate and USL255, a once‐daily extended‐release topiramate formulation

et al. 2013

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SUMMARYPurpose: Compare the pharmacokinetic (PK) profiles of immediate-and extended-release formulations of topiramate (TPM) in healthy subjects following multiple dosing, and evaluate maintenance of topiramate exposures after switching formulations. Methods: A randomized, open-label, single-center, twoway crossover, multiple-dose study comparing the steady-state PK profile of once-daily extended-release topiramate (USL255) to immediate-release topiramate (TPM-IR) administered twice-daily. The TPM PK profile was evaluated using standard PK parameters (e.g., AUC 0-24 , C max , C min ) as well as less common PK criteria such as fluctuation index (FI), peak occupancy time (POT), and percent coefficient of variation (%CV). In addition, partial AUC (AUC p ) analyses provided comparisons of the AUC profiles over predetermined time intervals between TPM-IR and USL255. Pharmacokinetic equivalence between formulations was defined as containment of the 90% confidence intervals (CIs) of the USL255/TPM-IR geometric least-squares mean (GLSM) ratio within the equivalence limits of 80-125%. The effect of switching between treatments was assessed by evaluating equivalence of PK parameters between the day prior to formulation switch and the day immediately following formulation switch. Maintenance of steady state after switching formulations was also evaluated by comparing the slope between C min values at formulation switch and 24 h postswitch. Tolerability was evaluated through adverse event monitoring, vital sign measurements, and clinical laboratory evaluations. Key Findings: USL255 was well tolerated and provided TPM plasma exposure equivalent to TPM-IR at various time intervals. USL255 also demonstrated a significantly lower C max (p < 0.001) and higher C min (p < 0.001), longer t max , lower %CV, and 26% decreased FI, as compared with TPM-IR. Further, switching between TPM-IR and USL255 did not affect TPM concentrations, including C min , immediately after transitioning and at steady state. Significance: As compared with TPM-IR, USL255 provided equivalent plasma exposure with an extended absorption profile. Therefore, USL255 offers a once-daily alternative to twice-daily TPM-IR, with reduced TPM fluctuations.

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FI = \frac{C_{\max} ‐ C_{\min}}{C_{avg}}

…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Comparative steady‐state pharmacokinetic evaluation of immediate‐release topiramate and USL255, a once‐daily extended‐release topiramate formulation

et al. 2013

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“…The controlledrelease formulation produced minimum (C min ) and mean (C mean ) serum lithium concentrations significantly higher than those of the immediate-release formulation, and a lower fluctuation of concentrations (%F). Knowing that the fluctuation is a measure of the effectiveness of sustained released formulation, 5,10 which has been usually related to a lower incidence of sideeffects, the results indicate that the controlled-release formulation could be a safe alternative for the patients' treatment. However, both formulations were similar regarding the maximum concentration produced, the opposite to what was expected for this kind of product.…”

Section: Discussionmentioning

confidence: 97%

“…However, this kind of formulation produces high lithium blood levels, which have been associated to side effects and intoxication originated from the product. 5 Alternatively, the modified or controlled-release formulations provide specific advantages over immediate-release formulations, due to decreased blood peaks secondary to a showed absorption rate. The elimination phase of the drug's decreasing curve is altered, causing an increase in the elimination half-life, allowing to the administration of a daily single dose instead of the traditional divided doses -two or three (b.i.d.…”

Section: Introductionmentioning

confidence: 99%

Bioavailability of immediate and controlled release formulations of lithium carbonate

Vismari

Pires

Benedito‐Silva

et al. 2002

Rev. Bras. Psiquiatr.

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INTRODUCTION/OBJECTIVES: Controlled-release lithium formulations were developed to minimize elevated blood peaks, related to side-effects and intoxications. However, there is little information about the bioavailability of the only controlled-release lithium formulation available in Brazil. The objective of this study was to compare the bioavailability of controlled-release and immediate-release lithium formulations, after single and multiple doses. METHODS: Twelve healthy volunteers received 900 mg of immediate-release or controlled-release lithium carbonate in single or multiple doses during 9 days. After single dose administration, the following parameters were analyzed for each formulation: maximum lithium concentration (Cmax); time to reach Cmax (t max); area under the curve of serum concentration versus time (AUC0-12 and AUC0-<FONT FACE=Symbol>¥</FONT>) and the elimination half-life (t1/2 elim.). After multiple doses, Cmax; t max; AUC0-12; mean (Cmean) and minimum drug concentration (Cmin) and degree of fluctuation (DF) were analyzed. A 90% confidence interval (90%CI) for the ratio between the AUCs for each formulation was constructed. RESULTS/DISCUSSION: Following single dose, the two formulations were bioequivalent; however, they were not after multiple doses. This fact could be a consequence of methodological limitations of lithium level's measurements since, following single dose, these levels could not be detected at time periods 24 and 48h in many volunteers, compromising the calculation of t1/2 elim ,and consequently of the AUC0<FONT FACE=Symbol>-¥</FONT> and the 90%CI to the ratio of these areas. Therefore, the bioequivalence found after single dose may be an unreliable result.

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“…Advantages of such systems include the maintenance of plasma drug concentrations in a therapeutically desired range (2), a reduction in toxic side effects (3), improved patience compliance (4), and a reduction in the required administration frequency (5). Typically the basis for such matrices are cellulose ether polymers such as hydroxypropyl methylcellulose (HPMC), which form a pseudogel layer on the surface of the tablet when exposed to water.…”

Section: Introductionmentioning

confidence: 99%

Toward Biorelevant Dissolution: Application of a Biphasic Dissolution Model as a Discriminating Tool for HPMC Matrices Containing a Model BCS Class II Drug

Phillips¹,

Pygall²,

Cooper³

et al. 2012

Dissolution Technol.

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The potential of a biphasic dissolution system to assist with the analysis of controlled-release (CR), Biopharmaceutics Classification System (BCS) Class II pharmaceutical products has been investigated. Use of a biphasic dissolution medium (aqueous/octanol) provided sink conditions and afforded complete dissolution of nifedipine formulated in a CR matrix tablet while maintaining the dosage form in an aqueous environment. This was not possible in a monophasic (aqueousonly) dissolution medium. Consequently, the biphasic model allowed the discrimination of three formulations containing different HPMC loadings while the monophasic medium did not. The performance of the formulations in conventional dissolution media incorporating the inorganic salt dibasic sodium phosphate, the surfactant sodium dodecyl sulfate (SDS), and ethanol as solubility modifiers was assessed. The addition of the salt and surfactant failed to produce complete discrimination in a predictive manner. The use of a hydroalcoholic medium comprising water and ethanol enabled the statistical discrimination of the three formulations but not as effectively as the biphasic medium.

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Steady‐State Lithium Blood Level Fluctuations in Man Following Administration of a Lithium Carbonate Conventional and Controlled‐Release Dosage Form

Cited by 17 publications

References 5 publications

Comparative steady‐state pharmacokinetic evaluation of immediate‐release topiramate and USL255, a once‐daily extended‐release topiramate formulation

Comparative steady‐state pharmacokinetic evaluation of immediate‐release topiramate and USL255, a once‐daily extended‐release topiramate formulation

Bioavailability of immediate and controlled release formulations of lithium carbonate

Toward Biorelevant Dissolution: Application of a Biphasic Dissolution Model as a Discriminating Tool for HPMC Matrices Containing a Model BCS Class II Drug

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