Implementing the 2017 Classification of Periodontal and Peri-Implant Diseases - how are we doing in the South West region of the UK?

Background A new world classification of periodontal diseases and conditions was developed in 2017 and implemented throughout the United Kingdom by the British Society of Periodontology and Implant Dentistry.Method A retrospective audit was undertaken at Bristol Dental Hospital (BDH) (December 2019 to March 2020) to assess uptake of the new classification in referral letters and its implementation by staff. In total, 75 consecutive new patient referrals seen at BDH were manually searched for diagnosis/classification. Additionally, the 75 most recent referrals where both the referring practitioner and BDH staff used the 2017 classification were analysed for agreeability.Results Within South West England, there was a positive uptake of the new classification in general practice, with 85% of referrals using the 2017 periodontal classification. Further, 98% of patients attending BDH for periodontology consultations were diagnosed using the 2017 classification. Results indicate 50.7% and 57.3% agreement for staging and grading, respectively, when comparing consultants to referring clinicians.Discussion The new classification has been widely conveyed to the profession and is being adopted quickly by specialists, general practitioners and dental health professionals. There is an underestimation of both stage and grade by referring practitioners, with 40% of referrals underestimating the stage and 38.7% underestimating the grade.

Distribution of zolmitriptan into the CNS in healthy volunteers: a positron emission tomography study.

OBJECTIVE: Triptans are highly effective in the treatment of migraine. Both central and peripheral mechanisms of action have been suggested. Until now, firm data about the passage of triptans into the CNS in humans have been lacking. The aim of the current study was to evaluate, using positron emission tomography (PET), the uptake and distribution of zolmitriptan into the CNS after intranasal administration. SUBJECTS AND METHODS: Eight healthy volunteers, five males and three females (mean ages 23 and 26 years, respectively), were included. Radioactive [carbonyl-11C]zolmitriptan was infused intravenously for 5 minutes on two occasions: once alone, and once 30-40 minutes after intranasal administration of unlabelled zolmitriptan 5 mg. PET was used to measure the concentration of labelled zolmitriptan in the brain, from the start of the tracer infusion for 90 minutes. Regional cerebral blood volume was determined with [15O]carbon monoxide. In addition, an MRI scan was performed to obtain anatomical information. The PET images were analysed quantitatively for different areas of the brain, generating [11C]zolmitriptan time-activity data corrected for circulating tracer activity. The rate of uptake of intranasal zolmitriptan into the CNS was estimated by kinetic modelling using the PET data. RESULTS: PET data from this study demonstrate a rapid dose-proportional uptake of [11C]zolmitriptan into the brain. Significant concentrations of [11C]zolmitriptan were found in all brain regions studied. Calculated CNS concentrations after intranasal zolmitriptan administration showed a gradual increase, reaching about 2 nM (0.5 microg/L) 30 minutes after administration and 3.5 nM (1.0 microg/L), or one-fifth of the plasma concentration, 1 hour after administration. Five minutes after zolmitriptan administration, the mean CNS concentration had already reached 0.5 nM, which is higher than in vitro values for initiation of the agonistic action on 5-HT(1B/1D) receptors. CONCLUSION: This study demonstrates by direct measurements that zolmitriptan enters the brain parenchyma in humans, achieving an uptake rate and concentration compatible with a central mode of action.

Preliminary studies of the pharmacokinetics and tolerability of zolmitriptan nasal spray in healthy volunteers.

Two preliminary studies of the pharmacokinetics and tolerability of zolmitriptan nasal spray were conducted, each involving 12 healthy volunteers. In study 1, an initial double-blind, dose escalation phase (placebo or 2.5, 5.0, or 10 mg zolmitriptan intranasally) was followed by an open crossover phase in which all subjects received 10 mg zolmitriptan as a nasal spray, tablet, and oral solution. In study 2, subjects received, on three separate occasions, zolmitriptan 2.5 mg as an intranasal solution at pH 7.4, at pH 5.0, and as an oral tablet. In study 1, plasma concentrations of zolmitriptan and its active metabolite, 183C91, were broadly dose proportional. Plasma concentrations of zolmitriptan were detected earlier following nasal spray administration than after either tablet or oral solution. Similarly, in study 2, zolmitriptan was absorbed more rapidly following nasal spray administration with detectable plasma concentrations 5 minutes after dosing. Plasma levels were maintained at a plateau between 1 and 6 hours postdose, then decreased with a half-life of approximately 3 hours. There was no statistically significant difference for AUG or C(max) values between the two nasal spray solutions or between nasal spray and oral formulations. Other pharmacokinetic parameters for zolmitriptan were similar between the formulations. Plasma concentrations of 183C91 were higher for the first 2 hours after oral than after nasal spray administration. All formulations of zolmitriptan were well tolerated.

Pharmacokinetics, dose proportionality, and tolerability of single and repeat doses of a nasal spray formulation of zolmitriptan in healthy volunteers.

The objective of this study was to investigate the pharmacokinetics, dose proportionality, and tolerability of a range of single and multiple doses of a nasal spray formulation of zolmitriptan in a randomized, double-blind, placebo-controlled, balanced, incomplete crossover study. Thirty healthy male or female volunteers received two of five dose levels of zolmitriptan nasal spray: 0 (placebo), 0.5, 1, 2.5, and 5 mg. At each level, treatment comprised a single dose on day 1 and two doses (separated by 2 h) on each of days 2, 3, and 4. Zolmitriptan was well tolerated, and symptoms were generally mild and of short duration. The most commonly reported adverse events were taste disturbance, paresthesia, hyperesthesia, headache, and nasal/throat discomfort. Volunteers generally reported fewer adverse events during the multiple-dose phase than after the single-dose phase. Zolmitriptan was detectable in plasma within 15 minutes, and t(max) was similar for each dose and after single and multiple dosing. Dose proportionality was shown for the C(max) and AUC of both zolmitriptan and its active metabolite, 183C91. Mean t1/2 for zolmitriptan and 183C91 was approximately 3 hours. It was concluded that the pharmacokinetics (C(max) and AUC) for both zolmitriptan and 183C91 was proportional to dose after both single and multiple dosing. Nasal spray zolmitriptan was well tolerated; the frequency and nature of adverse events did not increase after multiple dosing.

Zolmitriptan intranasal: a review of the pharmacokinetics and clinical efficacy.

Migraine is a common disabling neurological disorder, associated with headache, nausea, and on occasions vomiting. Zolmitriptan is a widely available serotonin 5HT(1B/1D) receptor agonist with a long track record in clinical studies and in the treatment of acute migraine. A nasal formulation has been developed that has clear evidence for local absorption, resulting in plasma drug concentrations within 2 minutes of dosing, central nervous system penetration 3 minutes later, and a significant efficacy benefit versus placebo 10 to 15 minutes after dosing. Intranasal zolmitriptan offers advantages to migraineurs, particularly those seeking a more rapid onset of effect without wishing to self-inject, or those with gastrointestinal upset. The comparison of pharmacokinetic and clinical data available from different formulations of zolmitriptan contributes both to the understanding of its mode of action and the characteristics required of an acute migraine treatment if it is to meet patient needs.

Blood-brain barrier penetration of zolmitriptan--modelling of positron emission tomography data.

Positron emission tomography (PET) with the drug radiolabelled allows a direct measurement of brain or other organ kinetics, information which can be essential in drug development. Usually, however, a PET-tracer is administered intravenously (i.v.), whereas the therapeutic drug is mostly given orally or by a different route to the PET-tracer. In such cases, a recalculation is needed to make the PET data representative for the alternative administration route. To investigate the blood-brain barrier penetration of a drug (zolmitriptan) using dynamic PET and by PK modelling quantify the brain concentration of the drug after the nasal administration of a therapeutic dose. [11C]Zolmitriptan at tracer dose was administered as a short i.v. infusion and the brain tissue and venous blood kinetics of [11C]zolmitriptan was measured by PET in 7 healthy volunteers. One PET study was performed before and one 30 min after the administration of 5 mg zolmitriptan as nasal spray. At each of the instances, the brain radioactivity concentration after subtraction of the vascular component was determined up to 90 min after administration and compared to venous plasma radioactivity concentration after correction for radiolabelled metabolites. Convolution methods were used to describe the relationship between arterial and venous tracer concentrations, respectively between brain and arterial tracer concentration. Finally, the impulse response functions derived from the PET studies were applied on plasma PK data to estimate the brain zolmitriptan concentration after a nasal administration of a therapeutic dose. The studies shows that the PET data on brain kinetics could well be described as the convolution of venous tracer kinetics with an impulse response including terms for arterial-to-venous plasma and arterial-to-brain impulse responses. Application of the PET derived impulse responses on the plasma PK from nasal administration demonstrated that brain PK of zolmitriptan increased with time, achieving about 0.5 mg/ml at 30 min and close to a maximum of 1.5 mg/ml after 2 hr. A significant brain concentration was observed already after 5 min. The data support the notation of a rapid brain availability of zolmitriptan after nasal administration.

Zolmitriptan nasal spray: advances in migraine treatment.

Zolmitriptan nasal spray was developed specifically to achieve fast, high effectiveness and to overcome many of the limitations associated with oral and sc migraine therapies. Pharmacokinetic studies have demonstrated a very rapid appearance of zolmitriptan in plasma as early as 5 minutes after intranasal dosing, with about 40% of peak plasma concentration (C(max)) being achieved within 10 to 15 minutes of dosing. Comparison of plasma concentration-time profiles of zolmitriptan and its active metabolite after oral and intranasal administration, together with PET scanning, clearly indicate direct absorption of zolmitriptan across the nasal mucosa after intranasal administration. The remainder of the dose is then swallowed and is absorbed through the gastrointestinal tract. In one blinded, randomized, placebo-controlled, multiple-attack study of zolmitriptan nasal spray, headache response was superior to placebo as early as 15 minutes after dosing (p < 0.05). In the zolmitriptan 5 mg treatment group, the primary end point of 2-hour headache response was achieved in 70% (300/427) of attacks versus 31% of attacks (119/389 attacks) in the placebo group (p < 0.001). Patients achieved a 2-hour headache response, had no recurrence, and used no additional or escape medications for up to 24 hours in 49% of attacks versus 14% of attacks in the placebo group (p < 0.001). Zolmitriptan 5 mg nasal spray was well tolerated. These data and those from other similar studies demonstrate that zolmitriptan nasal spray combines early, sustained efficacy and good tolerability, making it an optimal acute treatment for migraine.